Clinical Neuroscience

[INTERACTIONS BETWEEN THE MTHFR C677T AND MTHFR A1298C MUTATIONS IN ISCHAEMIC STROKE]

SZOLNOKI Zoltán, SOMOGYVÁRI Ferenc, SZABÓ Mihály, KONDACS András, FODOR Lajos, MELEGH Béla

MARCH 30, 2006

Clinical Neuroscience - 2006;59(03-04)

[Introduction - Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C mutations, being considered unfavourable genetic factors by causing elevated serum homocysteine levels, may be risk factors for cardiovascular disorders, including ischaemic stroke. In this study, the role of these two mutations in ischaemic stroke was examined. Patients and methods - Genetic and clinical data were analysed of 122 ischaemic stroke patients and 102 control subjects with no lesions by neuroimaging. Results - Neither of the two MTHFR mutations alone was found to be a significant genetic risk factor for ischaemic stroke. However, at least one MTHFR 677T allele combined with at least one MTHFR 1298C allele significantly increased the risk of ischaemic stroke (adjusted odds ratio: 3.39; p<0.001). Conclusion - The synergistic effect between the two MTHFR mutations may represent a new genetic stoke risk factor.]

COMMENTS

0 comments

Further articles in this publication

Clinical Neuroscience

[THE USE OF INTRAVENOUS IMMUNGLOBULIN IN THE TREATMENT OF AUTOIMMUNE NEUROMUSCULAR DISEASES]

MOLNÁR Mária Judit

[Intravenous immunglobulin given in autoimmune neuromuscular disorders modulates the immune system by complex actions, including, 1. the modification of the expression and function of Fc receptors, 2. interference with the activation of the complement and the cytokine network, 3. neutralisation of antiidiotypic antibodies, 4. effects on the activation, differentiation and effector functions of the T and B cells. Controlled trials have shown that intravenous immunglobulin is effective as first-line therapy in patients with Guillain-Barré syndrome and multifocal motor neuropathy. In case of steroid resistance or coexisting diabetes mellitus, intravenous immunglobulin can be the first line therapy in chronic inflammatory demyelinating polyneuropathy as well. As an alternative therapy it can be a second-line choice in dermatomyositis, myasthenia gravis, Lambert-Eaton myasthenic syndrome, and stiff person syndrome. While it has a remarkably good safety record for long term administration the following side effects have been observed: headache, skin rash, thromboembolic events and renal tubular necrosis. In some disorders, the appropriate dose and frequency of infusions that maintain a satisfactory therapeutic response is well defined on the basis of data of evidencebased medicine, whereas in others it still remains to be defined. For the analysis of pharmacoeconomical aspects and the mechanism(s) of response differences in the same disease categories, further studies are necessary.]

Clinical Neuroscience

[Functional consequences of basal ganglia pathologies]

BENICZKY Sándor

Clinical Neuroscience

[Reply on the vascular tunnel issue by right of the last word]

CSÓKAY András

Clinical Neuroscience

[PLASTICITY OF NOCICEPTION: RECENT ADVANCES IN FUNCTION-ORIENTED STRUCTURAL PAIN RESEARCH]

KNYIHÁR Erzsébet, CSILLIK Bertalan

[Traditional concept holds that the pain unit consists of three neurons. The first of these, the primary nociceptive neuron, starts with the nociceptors and terminates in the dorsal spinal cord. The second one, called spinothalamic neuron, crosses over in front of the central canal and connects the dorsal horn with the thalamus. The third one, called thalamo- cortical neuron, terminates in the “pain centres” of the cerebral cortex. While this simplistic scheme is useful for didactic purposes, the actual situation is more complex. First, in the periphery it is only nociception that occurs, while pain is restricted to the levels of thalamus and the cortex. Second, pain results from interactions of excitation and inhibition, from divergence and convergence and from attention and distraction, in a diffuse and plastic system, characteristic for all levels of organization. This study describes the major cytochemical markers of primary nociceptive neurons followed by the presentation of recent data on the functional anatomy of nociception and pain, with special focus on the intrinsic antinociceptive system and the role of nitrogen oxide, opiate receptors, nociceptin and nocistatin. In addition to the classic intrinsic antinociceptive centres such as the periaqueductal gray matter and the raphe nuclei, roles of several recently discovered members of the antinociceptive system are discussed, such as the pretectal nucleus, the reticular formation, the nucleus accumbens, the nucleus tractus solitarii, the amygdala and the reticular thalamic nucleus, this latter being a coincidence detector and a centre for attention and distraction. The localisation of cortical centres involved in the generation of pain are presented based on the results of studies using imaging techniques, and the structural basis of corticospinal modulation is also outlined. Seven levels of nociception and pain are highlighted where pharmacological intervention may be successful, 1. the peripheral nociceptor, 2. the spinal ganglion, 3. the multisynaptic system of the dorsal horn, 4. the modulatory system of the brain stem, 5. the antinociceptive system, 6. the multisynaptic system of the thalamus, and 7. the cortical evaluating and localisation system that is also responsible for descending (inhibiting) control. The many levels of nociception and pain opens new ways both for pharmacological research and the general practitioner aiming to alleviate pain.]

Clinical Neuroscience

[SPECTRAL EEG-CHARACTERISTICS OF SUBCORTICAL ISCHEMIC BRAIN LESION- A CASE STUDY]

MOLNÁR Márk, CSUHAJ Roland, HORVÁTH Szabolcs, VASTAGH Ildikó, GAÁL Zsófia Anna, CZIGLER Balázs, BÁLINT Andrea, NAGY Zoltán

[Introduction - Although the EEG-changes caused by ischemic stroke are well known, data of the literature are rather ambiguous. The EEGfindings recorded in a patient with a unilateral subcortical ischemic lesion are evaluated with special emphasis related to the effect of the dynamics caused by eyes opening. Participants and methods - Data recorded from a patient (54 years old male with a completed stroke involving the frontal and parietal subcortical region in the left side) were compared to those of a control group (12 healthy age matched subjects). Absolute and relative frequency spectra, theta/beta quotients, the interaction index characterizing the effect of eyes opening and the symmetry index were calculated from the EEG recorded in eyes closed and eyes open conditions. Data of the patient were compared to those recorded in the control group on the basis of 95% confidance intervals. Results - Irrespective of the recording conditions the predominance of slow activity and the increase of theta/beta quotients were found in the absolute frequency spectra. The increase of beta1 and beta2 frequency bands following eyes opening on the side of the lesion were found to be less obvious than that seen on the intact side and that observed in the control group. With respect to the interaction index related to the side differences caused by eyes opening the change of the beta2 frequency band was found to be the most conspicuous. The symmetry index underscored the predominance of slow (delta, theta, alpha1) frequencies on the lesion side, and that of the fast (beta1, beta2) frequencies on the intact side in both recording conditions. Conclusions - Localized lesion of the white matter without cortical damage can cause the predominance of slow activity and decrease of the fast frequency bands on the side of the lesion which can be shown by the absolute frequency spectra and is revealed by the symmetry index. The lack of functional reactivity of the fast frequencies in the side of the lesion can clearly be seen in the change of relative spectra following eyes opening and on the basis of the calculation of the interaction index reflecting the dynamics of side differences.]

All articles in the issue

Related contents

Clinical Neuroscience

Hyperhomocysteinemia in female migraineurs of childbearing ages

ALEMDAR Murat, SELEKLER Macit Hamit

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

[Application of diffusion weighted imaging in neuroradiology]

BARSI Péter

[Diffusion weighted magnetic resonance (MR) imaging is available on all modern MR scanners. It depicts the motion of water molecules in the brain tissue and intracranial foreign tissues and provides information on changes in the proportion of intra- and extracellular space and the characteristics of foreign intracranial tissues and fluids. It is of utmost importance eg. in the diagnostics and differential diagnostics of acute ischaemic brain lesions, the diagnostics of inflammatory brain processes and in the differential diagnostics of intracranial space-occupying lesions. The examination method of short scanning and post-processing time must be completed with the apparent diffusion coefficient (ADC) maps and it is indispensable in the everyday neuroradiological diagnostics. Diffusion tensor imaging and tractography are able to depict the white matter tracts. They require a longer scanning and post-processing time and have several technical problems yet to be solved, but they provide help in their current state e.g. in the surgical planning of intracranial space-occupying lesions.]

Hypertension and nephrology

[Stroke incidence and prevalence in the world]

KÉKES Ede

[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.]

Lege Artis Medicinae

[The safety of rosiglitazone - Lessons from the RECORD study]

HALMOS Tamás

[The international RECORD study team evaluated the safety of the oral antidiabetic drug rosiglitazone, after contradictory reports of its unfavourable cardiovascular adverse effects, in combination with sulfonyureas and metformin. The drug didn’t increase cardiovascular morbidity and overall mortality compared with standard blood sugar lowering drugs. However, it increased the risk of heart failure, and, in women, the risk of limb fractures. Keeping in mind the strict contraindications, the drug can still be prescribed, as glitazones have effective blood sugar lowering and insulin-sensitizing effects.]

Clinical Neuroscience

[Neuroprotection in brain ischemia - doubts and hopes]

ZÁDOR Zsolt, BENYÓ Zoltán, LACZA Zsombor, HORTOBÁGYI Tibor, HARKÁNY Tibor

[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.]