Clinical Neuroscience

[ANIMAL MODELS OF HUNTINGTON’S DISEASE]

GÁRDIÁN Gabriella

NOVEMBER 30, 2006

Clinical Neuroscience - 2006;59(11-12)

[Huntington’s disease is an autosomal dominantly inherited progressive neurodegenerative disorder. The main symptoms are choreiform, involuntary movements, personality changes and dementia. Huntington’s disease is a member of a group of diseases caused by CAG repeat expansions. One research aim is to determine the earliest molecular changes associated with Huntington’s disease. There is no possibility for this in humans, but various early changes have been identified in an animal model of Huntington’s disease. They are constructed by excitotoxin causing striatal lesion, or mitochondrial toxins inducing energy impairment, or by generating transgenic mice.]

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Clinical Neuroscience

[THORACIC MENINGOCELE]

FEKETE Tamás Fülöp, VERES Róbert, NYÁRY István

[Herniation of the meninges through a defect of the spinal canal is a spinal meningocele, and is usually located dorsally in the lumbosacral region. Meningoceles are usually part of a complex developmental disorder, or of a systemic disease, or it can be iatrogenic, as well. We report a very rare case of a true anterior thoracic meningocele.]

Clinical Neuroscience

[Introduction]

VÉCSEI László

Clinical Neuroscience

[THE MODULATORY EFFECT OF ESTROGEN ON THE CAUDAL TRIGEMINAL NUCLEUS OF THE RAT IN AN ANIMAL MODEL OF MIGRAINE]

VARGA Hedvig, PÁRDUTZ Árpád, TAJTI János, VÉCSEI László, JEAN Schoenen

[Migraine is one of the most common neurological disorder affecting up to 14% of the population. The disease shows sexual dimorphism, thus gonadal steroids may play an important role in its patophysiology. One model of migraine headache is the systemic administration of nitric oxide (NO) donor nitroglycerin (NTG), which triggers a delayed attack without aura in many migraine patients but not in healthy volunteers. NTG is also able to activate the neurons of the caudal trigeminal nucleus in the rat. In our review we summarise the effect of NTG on the expression of some molecules, in the superficial laminae of the spinal portion of trigeminal nucleus caudalis, which play an important role in the pathomechanism of headaches, and the modulatory effect of chronic estradiol treatment. Our data show that NTG was able to modify all the examined substances in the caudal trigeminal nucleus, while chronic estradiol treatment abolished this effect. These data may help to understand the mechanisms by which estrogens influence trigeminal nociception and how nitric oxide triggers migraine attacks.]

Clinical Neuroscience

[CLINICAL ANALYSIS OF PATIENTS WITH PERIPHERAL FACIAL PALSY]

ILNICZKY Sándor

[symptoms. In two thirds of the cases the cause is unknown, this is called “idiopathic peripheral facial palsy or Bell’s palsy”, but several different diseases have to be considered in the differential diagnosis. In this paper we reviewed the case histories of 110 patients treated for “peripheral facial palsy” in the Department of Neurology, Semmelweis University, Budapest in a five year period, 2000-2004. We studied the age, gender distribution, seasonal occurance, comorbidities, sidedness, symptoms, circumstances of referral to the hospital, the initial diagnoses and therapeutic options. We also discuss the probable causes and consequences of diagnostic failures. Results: the proportion of males and females was equal. There was no considerable difference between sexes regarding agedistribution. Of the 110 patients 106 was diagnosed with idiopathic Bell’s palsy, three cases with otic herpes zoster and one patient with Lyme disease. In our material, peripheral facial palsy was significantly more frequent in the cold period of late autumn, winter, and early spring. Diabetes mellitus and hypertension were more frequent than in the general population. 74% of the patients were admitted within two days from the onset of the symptoms. In 37% preliminary diagnosis was unavailable. In 15% cerebrovascular insult was the first, incorrect diagnosis, the correct diagnosis of “Bell’s palsy” was provided only in 16%. The probable causes of diagnostic failures may be the misleading symptoms and accompanying conditions. We examined the different therapies applied and reviewed the literature in this topic. We conclude that intravenous corticosteroid treatment in the early stage of the disease is the therapy of choice.]

Clinical Neuroscience

[COMPLEX NON-INVASIVE HEMODYNAMIC SYSTEM FOR THE EVALUATION OF VASCULAR STATUS]

CSAPÓ Krisztina, BAJKÓ Zoltán, MOLNÁR Sándor, MAGYAR Tünde, CSIBA László

[The vascular diseases (myocardial infarct, stroke, peripheral occlusive disease) have a common pathophysiological background, the arteriosclerosis, that impairs the autoregulation of cerebral vessels, decreases the endothel mediated flow in the peripheral vessels. Therefore the assessment of the vascular damage or the follow-up of therapy need a complex and simultaneous approach. Currently the morphological and functional changes in the vascular system can be investigated with separated measuring systems, focusing either to cardiac or cerebral parameters (intermittent blood pressure measurement, ECG, cerebral blood flow by transcranial Doppler e.g.). Our purpose is to establish a complex non-invasive system for the simultaneous measurement and comparison of cardiac/cerebral/periheral hemodynamics. The hemodynamic parameters in hypertensive patients are examined with transcranial Doppler and cardiac monitoring during tilt-table test. Intima-media thickness, flow-mediated dilatation in brachial artery, augmentation index and pulse wave velocity are also measured. The measurement will be repeated after 6 and 12 months follow-up. Our preliminary results are similar to those found in the literature, that proves the reliability of our complex noninvasive hemodynamic system. It is assumed, that 12 months antihypertensive therapies with ACE inhibitors, calciumantagonist etc. might result in different effects on different vascular parameters. Our system enables the individualization of antihypertensive therapy.]

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Evaluation of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in essential tremor

TAK Zeynal Abidin Ali, SENGUL Yildizhan

Introduction - Although essential tremor (ET) is the most common cause of tremor, the pathology and underlying mechanisms have not fully understood yet. In addition to kinetic tremor, patients may present several types of tremor, gait ataxia, hearing deficits and eye movement abnormalities. Non-motor symptoms and signs have also added to definition of ET. There is significant evidence indicating the neurodegenerative nature of the disease. New studies indicate that inflammation may have a place in the etiology. The neutrophil-to lymphocyte ratio (NLR) and the platelet-to lymphocyte ratio (PLR) have recently begun to be used as a marker of systemic inflammation. Our study aims at finding a clue for systemic inflammation in ET. Methods - 67 patients with ET and 40 healthy controls were recruited for the study. The total white blood cells (WBC), absolute neutrophil count, lymphocyte count and platelet count were retrieved. The NLR was calculated by dividing the neutrophil count by the lymphocyte count and the PLR was calculated by dividing the platelet count by the lymphocyte count. Results - Patient and control groups were similar in terms of age and gender. The mean age of patient group was 25.29 ± 8.24 years and that of control group was 26.77 ± 6.73 years. The NLRs were 1.85 ± 0.58 in the patient group and 1.96 ± 0.53 in the control group. For the patient group and the control group the PLRs were 103.52 ±32.80 and 91.26 ± 31.57 respectively. There were no statistically significant differences between the participants for both NLR and PLR. Conclusion - The pathophysiological mechanism for essential tremor (ET) remains unclear. However, there is an increasing amount of research being conducted on the subject. Discussions about ET’s definition as a neurodegenerative disease are ongoing. Although previous studies showed that neuroinflammation could be a part of etiology of disease, this study has failed to demonstrate systemic inflammation in ET.

Clinical Neuroscience

Gray matter atrophy in presymptomatic Huntington’s patients

KIRÁLY András, KINCSES Zsigmond Tamás, SZABÓ Nikoletta, TÓTH Eszter, CSETE Gergő, FARAGÓ Péter, VÉCSEI László

Background - Huntington’s disease is a progressive disease in which neurodegeneration is on-going from the early presymptomatic phase. Development of sensitive biomarkers in this presymptomatic stage that are able to monitor the disease progression and test the efficacy of putative neuroprotective treatments are essential. Methods - Seven presymptomatic Huntington mutation carriers and ten age-matched healthy controls were recruited. Six of the patients participated in a 24 months longitudinal study having MRI scans 12 and 24 months after the baseline measurements. High resolution T1 weighted images were carried out and voxel based morphometry was used to analyse the data. Apart of group differences, correlation of CAG repeat number with focal cortical thickness and with global gray matter volume was calculated. Results - Focal cortical atrophy was found bilaterally in the superior temporal sulcus and in the left middle frontal gyrus in presymptomatic Huntington patients in whom no sign of cognitive or motor deterioration was detected. Global gray matter atrophy (p<0.048) and decreased total brain volume was found. The number of CAG triplets showed no correlation with the focal gray matter atrophy and total brain volume. Strong correlation between the CAG repeat number and global gray matter volume was found (p<0.016). Conclusion - Cortical atrophy is apparent in the early, presymptomatic stage of the disease. With further validation in large patient sample atrophy measure could be biomarker of disease progression and putatively of neurodegeneration.

Clinical Neuroscience

[Diffusion MRI measured white matter microstructure as a biomarker of neurodegeneration in preclinical Huntington’s disease]

KINCSES Tamás Zsigmond, SZABÓ Nikoletta, TÓTH Eszter, ZÁDORI Dénes, FARAGÓ Péter, NÉMETH Dezsõ, JANACSEK Karolina, BABOS Magor, KLIVÉNYI Péter, VÉCSEI László

[Background - Huntington’s disease is a progressive neurodegenerative disease, genetically determined by CAG trinucleotide expansions in the IT15 gene. The onset of the symptoms is related to the number of CAG triplets. Because the patients are asymptomatic in the early phase of the disease, in vivo biomarkers are needed to follow up the neurodegeneration and to test putative neuroprotective approaches. One such promising biomarker is the diffusion MRI measured microstructural alteration of the white matter. Methods - Seven presymtomatic, mutation carriers and ten age-matched healthy controls were included in the study. Diffusion parameters were compared between groups and correlated with measures describing neurodegeneration. In order to reduce the possible misregistration bias due to atrophy the analysis was restricted to the core of each fibre bundles as defined by maximal fractional anisotropy (Tract- Based Spatial Statistics). Results - Decreased fractional anisotropy, along with increased mean, parallel and perpendicular diffusivity was found in white matter tracts, mainly in the corpus callosum. An inverse correlation was detected between the fractional anisotropy and neurodegeneration score (derived from the number of CAG triplets and the patient age) from the areas of the left precentral gyrus, frontal lobe, corpus callosum and the capsula extrema. Altered diffusion parameters are promising biomarkers of the neurodegeneration in Huntington’s disease.]