Clinical Neuroscience

[Frontotemporal dementia - Part II Differential diagnosis, genetics, molecular pathomechanism and pathology]

GALARIOTIS Vasilis, BÓDI Nikoletta, JANKA Zoltán, KÁLMÁN János

JULY 10, 2005

Clinical Neuroscience - 2005;58(07-08)

[This is a comprehensive paper in three parts covering history, prevalence, clinical forms, differential diagnosis, genetics, molecular pathomechanism, pathology, clinical diagnosis and treatment of frontotemporal dementia (FTD). The second part focuses on the differential diagnosis, genetics, molecular pathomechanism and pathology. The clinical diagnosis of frontotemporal dementia is based on the presence of a prominent disturbance of the executive function and of frontal lobe syndrome or a progressive aphasic syndrome without severe global cognitive impairment. Of other dementias, it is primarily Alzheimer’s disease that it should be differentiated from, but other psychiatric disorders must also be ruled out. The disease has familial and sporadic forms. Recent identification of mutations in the gene encoding the microtubule-associated tau protein in the inherited frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) has demonstrated that various tau dysfunctions can lead to neurodegeneration. Tau gene mutations have varied effects on the biology and function of the protein. This heterogeneous pathomechanism explains the wide range of clinical and neuropathological features observed in the FTDP-17. Tau and ubiquitin antibodies can be detected by sensitive immunohistochemical methods. The diagnosis of FTD should be based on neuropathological examination, and this is also the only method by which it can be definitely differentiated from other types of dementias.]



Further articles in this publication

Clinical Neuroscience


Clinical Neuroscience

[Increasing cerebral perfusion pressure in serious cranial injury - contradictory effects of dopamine]

BARZÓ Pál, CZIGNER Andrea, ANTHONY Marmarou, ANDREW Beaumont, DEÁK Gábor, PANOS Fatouros, FRANK Corwin

[Background - Management of cerebral perfusion pressure is an important element of the treatment of traumatic brain injury. Vasopressors are accepted as a method of choice to increase mean arterial blood pressure and thus cerebral perfusion pressure in the face of rising intracranial pressure. There are, however, some unresolved issues and potential risks to this therapy. Matherial and methods - This study therefore examines the effects of dopamine on physiological changes as well as on brain edema and water content that can be readily assessed by MRI/MRS in 1. a rodent model of rapidly rising intracranial pressure, caused by diffuse injury with secondary insult and 2. a model of cortical contusion. Results - Dopamine was capable of restoring cerebral perfusion pressure in the model of rapidly rising intracranial pressure. However, this was associated with only a partial restoration of cerebral blood flow. In the brain tissue two profiles of change in the apparent diffusion coefficient of water (ADCw) were seen; one in which ADCw recovered to baseline, and one in which ADCw remained persistently low. Despite that dopamine did not alter these profiles, MRI-assessed tissue water content was increased four hours after injury and dopamine increased cerebral water content in both subgroups of injury, especially in the subgroup with a persistently low ADCw (p<0,01). In the contusion group dopamine significantly worsened the edema both in the injured and in the contralateral area of hippocampus and temporal cortex even though the ADCw values did not change, except for the contralateral hippocampus, where both water content and ADCw values rose with treatment, suggesting extracellular accumulation of water. Conclusion - The results suggest that dopamine has a double effect - while it temporarily and partially restores cerebral blood perfusion, at the same time it induces an increase in brain swelling and thus an increase in intracranial pressure in some cases. It is possible that in a subgroup of patients vasopressor treatment leads to an opposite effect several hours later. Vasopressor therapy in the clinical setting therefore should be cautiously applied.]

Clinical Neuroscience

[125I brachytherapy of pineal parenchymal tumours]

JULOW Jenő, VIOLA Árpád, MAJOR Tibor, VALÁLIK István, SÁGI Sarolta, MANGEL László, KOVÁCS Rita Beáta, HÁVEL János, KISS Tibor

[Introduction - Pineal parenchymal tumours make up 0,3% of all brain tumours. Stereotactic biopsy has by now become an indispensable method to detect these tumours and it can be safely performed. Patients and method - Two patients with pineoblastoma were treated with 125I brachytherapy. The MRI and CT images taken 15 and 18 months after irradiation showed significant tumour shrinkage. Results - Tumour volume was 0.76 cm3 in the control CT image in Case 1, a shrinkage by 73% compared to 2.87 cm3 measured at the time of planning the interstitial irradiation. In Case 2, tumour volume measured on the control MRI examination was 0.29 cm3 as opposed to 1.27 cm3 of original tumour volume, which represents a 77% shrinkage. Conclusion - The insertion of isotope seeds was performed at the same time as the biopsy, because thus the knowledge of the histological diagnosis could spare the patients from a second stereotactic intervention. The CT- and image fusion guided 125I stereotactical brachytherapy is a procedure that can be dosimetrically precisely planned and surgically accurately and safely performed.]

Clinical Neuroscience

[The role of transcranial magnetic stimulation in the investigation of the human motor system]

ARÁNYI Zsuzsanna

Clinical Neuroscience



[Introduction - While it is several decades ago that electrophysiological studies in the early stages after an ischaemic stroke revealed spontaneous activity in the affected muscles, today few data are available on the peripheral changes in later stages after a cerebrovascular event. The aim of this study was to detect electrophysiological signs that could indicate changes at the motor unit level occurring within a longer post-stroke period. Patients and methods - Forty-four patients who had developed hemiparesis after an ischaemic stroke in the area of the middle cerebral artery were involved in the study. Motor and sensory nerve conduction studies and electromyography were carried out on each side on six nerves and in five muscles respectively. Values between the affected and unaffected side were compared by statistical methods. Results - In patients with hemiparesis present for less then nine months, low M wave amplitudes, fibrillation potentials and an increased number of complex motor unit potentials were found on the affected side; in patients with symptoms present for more then nine months the mean duration and size index of the motor unit potentials in the paretic abductor digiti minimi muscle were increased. These data suggest a process of neurogenic type. The signs of distal axonal damage observed in the early period after stroke have been replaced later by chronic neurogenic changes. These changes could be the consequence of spinal motor neuron damage and axonal transport disturbance due to the loss of supraspinal trophic inputs. Conclusion - The correlation between the extent of electrophysiological changes and of the central motor deficit of the patient indicates the importance of delaying this process by appropriate rehabilitation procedures.]

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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.]

Clinical Neuroscience

Validation of the Hungarian version of the Test Your Memory

KOLOZSVÁRI Róbert László, KOVÁCS György Zoltán, SZŐLLŐSI József Gergő, HARSÁNYI Szilvia, FRECSKA Ede, ÉGERHÁZI Anikó

Concerns regarding the projected prevalence of Alzheimer’s disease (AD) over the next several decades have stimulated a need for the detection of AD in its earliest stages. A self-administered cognitive test (Test Your Memory, TYM) is designed as a short, cognitive screening tool for the detection of AD. Our aim was to validate the Hungarian version of the Test Your Memory (TYM-HUN) test for the detection of AD. The TYM-HUN was applied in case of individuals aged 60 years or more, 50 patients with AD and 50 healthy controls were recruited into the study. We compared the diagnostic utility of the Hungarian version of the TYM in AD with that of the Mini-Mental State Examination (MMSE). The sensitivity and specificity of the TYM-HUN in the detection of Alzheimer’s disease were determined. The patients with AD scored an average of 15.5/30 on the MMSE and 20.3/50 on the TYM-HUN. The average score achieved by the members of the healthy control group was 27.3/30 on the MMSE and 42.7/50 on the TYM. The total TYM-HUN scores significantly correlated with the MMSE scores (Spearman’s rho, r=0.8830; p<0.001). Multivariate logistic regression model demonstrated that a one-point increase in the TYM score reduced the probability of having AD by 36%. The optimal cut-off score on the TYM-HUN was 35/36 along with 94% sensitivity and 94% specificity for the detection of AD. The TYM has a much wider scoring range than the MMSE and is also a suitable screening tool for memory problems, furthermore, it fulfils the requirements of being a short cognitive test for the non-specialists. The TYM-HUN is useful for the detection of Alzheimer’s disease and can be applied as a screening test in Hungarian memory clinics as well as in primary care settings.

Clinical Neuroscience

[Lack of associations between CLU and PICALM gene polymorphisms and Alzheimer’s disease in a Turkish population]

SEN Aysu, ARSLAN Mehtap, ERDAL Emin Mehmet, AY Izci Ozlem, YILMAZ Gorucu Senay, KURT Erhan, ARPACI Baki

[Background and purpose - To investigate the association between the rs11136000 single nucleotide polymorphism (SNP) of the clusterin (CLU) gene, the rs541458 and rs3851179 SNPs of the phosphatidylinositol-binding clathrin assembly protein (PICALM) gene and Alzheimer’s disease (AD) in a Turkish population, and to determine whether there are any relationships between the CLU and the PICALM genotypes and behavioral and psychological symptoms of dementia (BPSD) in the Turkish population. Methods - One-hundred and twelve AD patients and 106 controls were included in this study. BPSD were evaluated by the Behavioral Pathology in Alzheimer’s Disease Rating Scale (BEHAVE-AD). SNPs in the CLU and the PICALM gene were genotyped by Real-Time PCR. Genotype distributions were assessed for the groups of patients and controls, for the patient groups with and without each BPSD, and “No BPSD” and “BPSD”. Results - The CLU and the PICALM genotypes were similar in the AD and control subjects, and the groups with and without each BPSD. There were also no significant differences between the “No BPSD” and the “BPSD” groups for the PICALM genotypes, but even without a statistical significance, it is notable that none of the “No BPSD” patients had genotype pattern CLU-rs11136000-TT, and the female subjects with genotype pattern CLU-rs11136000-TT had higher mean score of BEHAVE-AD. Conclusion - This study claims that investigated SNPs are not genetic risk factors for AD in a Turkish population. In addition, the rs541458 and rs3851179 of PICALM SNPs are not related to development of BPSD, but the rs11136000 of CLU SNP might be related to development of BPSD in AD female Turkish subpopulation.]

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.]

Lege Artis Medicinae


MŰZES Györgyi

[The cyclooxygenase (COX) metabolic pathway and prostaglandin production appear to play a causal role in the promotion and progression of human cancers. Recently COX-2 has received a great deal of interest since it is frequently overexpressed in a wide spectrum of cancers and precancerous lesions. Furthermore, elevated production of prostanoids (particularly PGE2) via COX-2 is associated with several pro-carcinogenic effects including increased proliferation, apoptosis resistance, tumor neoangiogenesis and invasiveness, host immunosuppression, and altered xenobiotic metabolism. Inhibitors of COX-1 and COX-2 (aspirin and most other nonsteroidal anti-inflammatory drugs) and of COX-2 alone (e.g. coxibs) have shown cancer preventive efficacy in epidemiological studies, experimental studies and in human clinical trials. Due to their improved side effect profile, COX-2 selective inhibitors appear to hold substantial promise for long-term administration in the setting of cancer prevention. Emerging data suggest that these agents may have potential in cancer treatment as well. In addition recent results indicate that COX-2 enzyme is also overexpressed in inflammatory processes of the central nervous system, e.g. in Alzheimer’s disease, so its suppression could offer a possible new therapeutic strategy even in the prevention and treatment of Alzheimer’s disease.]