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



[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.]

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

[Investigation of cerebral autoregulation in Parkinson’s disease]


[Background and purpose - The frequent orthostatic intolerance in Parkinson’s disease could be the consequence of cardiovascular autonomic failure and/or a damaged cerebral autoregulation (AR). To clarify this question the regulation of cerebral circulation was investigated by polygraphic method. Methods - On a tilt table simultaneous and continuous registrations were made of MCA velocity (VMCA) by transcranial Doppler, arterial blood pressure by non-invasive method, and end-tidal CO2, in supine and in tilted positions of 10°, 30°, 70° grades. The cerebral autoregulation was characterized by the slope of the curve of the arterial blood pressure at the level of the Willis-circle (BPW, as MCA perfusion pressure) plotted against the MCA velocity, achieved by linear regression (y=ax+b function, a=AR, or index of autoregulation). Patients - The data of 17 parkinsonian patients (PP) and eight age-matched controls (C) were analyzed. Results - The decrease of blood pressure in parkinsonian patients was significantly lower than in the controls when supine position was restored from 70° (ΔABP 70°-0°PP= -3.1±7.5 Hgmm; ΔABP 70°-0C°=-11.1±7.3 Hgmm; p<0.05), which suggests a damage to the sympathetic cardiovascular system. A disturbance of the cerebral autoregulation in patients was suggested by a progressively decreasing MCA average velocity (VMCA) during graded tilt, which was significiant at 70° (ΔVACM=9.8±8.82% cms-1; pCPP <0,05), and by a higher slope of pressure-velocity curve (ARC=0.143±0.125% cms-1/Hgmm; ARPP=0.38±0.25% cms-1/Hgmm; pC-PP<0.05). Conclusions - The results show that the cerebral blood flow of patients is more dependent on perfusion pressure compared to healthy controls. The disturbance of the sympathetic cardiovascular system and of cerebral autoregulation could be the consequence of a damage to the postganglionic structures in Parkinson’s disease. These results could explain the frequent orthostatic intolerance of patients even with normal blood pressure.]

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

[Stiff-person syndrome - two Hungarian cases and review of the literature]

LENGYEL András, LAKOS Gabriella, SIPKA Sándor, HEGEDÛS Katalin

[The stiff-man syndrome is a rare neurological disorder characterized by progressive stiffness of the axial muscles and co-contraction of agonist and antagonist muscles sometimes accompanied by involuntary sudden muscle spasms. The disease is thought to be caused by immunological changes leading to a GABA transmission disturbance, but the precise pathogenesis is not clear. Two Hungarian cases are presented in this article accompanied by a review of the literature. The aim of the paper is to call the attention on this presumably underdiagnosed disease. The diagnostic laboratory tests of the disease are available in Hungary.]

All articles in the issue

Related contents

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.]

Lege Artis Medicinae

[Gastrointestinal stromal tumor]


[Gastrointestinal stromal tumors were subject of much controversy in the last decades. This type of tumors was delineated from the leiomyoma - leiomyosarcoma group. GISTs show variable histological picture, moreover, they are capable of dual (neurogen and myogen) differentiation as it is proved by immunohistochemical and ultrastructural studies. These tumors have relatively good prognosis, only 10-30% of them is malignant, although it is difficult to predict their behaviour in a given case. The most reliable signs of malignancy - cytological pleoimorphism, high mitotic activity, proliferation index above 10 %, and aneuploid DNA content - are generally accepted. The treatment of choice is excision, but not enucleation. Radical surgery is not necessary, since lymph node metastasis is exceptionally rare. Further investigations revealed electronmicroscopical and immunohistochemical (CD 34, CD 117) similarities of tumor cells and interstitial cells of Cajal (ICC) located in the wall of the bowel. The results of these investigations led to the theory that cells of GIST and ICCs are of the same stem cell origin. Molecular genetic studies are also of great help in the differential diagnosis and in predicting the prognosis of GISTs. Mutations in the c-kit gene can not be detected in leiomyomas, so they are thougt to be specific for GISTs. Mutation of exon 11. of chromosome 4. is observed only in malignant GISTs.]

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.]