Clinical Neuroscience

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


JULY 30, 2015

Clinical Neuroscience - 2015;68(07-08)


[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.]



Further articles in this publication

Clinical Neuroscience

[Neurointerventional treatment of acute ischemic stroke: the Kaposvár experience]

RADNAI Péter, SZŐTS Mónika, RÁDAI Ferenc, HORVÁTH Gyula, VARGA Csaba, FOGAS János, SZÖRÉNYI Péter, HORVÁTH Zoltán, BAJZIK Gábor, MOIZS Mariann, REPA Imre, NAGY Ferenc, VAJDA Zsolt

[Aim of the study - In the present study, we report procedural and mid-term functional outcome data on the first 50 neurointerventional treatments of acute ischemic stroke in the Kaposi Mór County Hospital, Kaposvár, Hungary. Materials and methods - Endovascular recanalization of occluded large cervical and intracranial arteries was performed following an unsuccessful intravenous lysis or when intravenous lysis was contraindicated. A control cohort was retrospectively formed by analyzing data of 16 patients who has been unsuccesfully treated with iv. lysis before neurointervention was available in our hospital. Results and conclusion - Recanalization rate was 84% and major complication rate was 2% in the neurointerventional group. Mid-term good functional outcome, defined as mRS 0-2, was achieved in 44% in the neurointerventional and in 13% in the intravenous lysis group, after 11.5 and 39.7 months follow-up period, respectively. Subgroup analysis revealed patient age as the strongest predictive factor of good functional outcome. Our data shows that neurointerventional treatment of acute ischemic stroke gives substantially improved functional outcome, in accordance with the results of the recently published international randomized trials.]

Clinical Neuroscience

Thrombocytopenia with gabapentin usage

ATAKLI Dilek, YUKSEL Burcu, AK Dogan Pelin, SARIAHMETOGLU Hande, SARI Hüseyin

Gabapentin is an antiepileptic drug approved for adjunctive therapy for partial seizures. We report a case of a patient who had thrombocytopenia with the dose of 2400 mg/day of gabapentin. The causal relationship between gabapentin and thrombocytopenia was revealed by dramatic increase in thrombocyte count following the cessation of the gabapentin treatment. To our knowledge, this is the first case report with a hematopoietic side effect of gabapentin.

Clinical Neuroscience

[LGI1 encephalitis: the first Hungarian patient]

SZŐTS Mónika, MARTON Annamária, ILLÉS Zsolt, BAJZIK Gábor, NAGY Ferenc

[In the recent years, it has been increasingly recognised that in a group of limbic encephalitis antibodies are directed against the scaffolding protein LGI1 (Leucine-rich glioma inactivated 1), which is part of the voltage gated potassium channel (VGKC) complex on neural synapses. Patients present with seizures and subacute history of neuropsychiatric symptoms, including psychosis and changes in memory, cognition, behaviour. Faciobrachial dystonic seizures can be observed, which are highly characteristic for LGI1 encephalitis. MRI shows medial temporal abnormalities in more than half of the cases. CSF evaluation is usually normal. Hyponatremia is frequently associated and may confuse the initial diagnosis. Early recognition and prompt initiation of immunotherapies are of great importance. The clinical improvements often correlate with the antibody levels. We present the case of a 64-year old man, who responded quickly to plasma exchange and major improvement was noted within few weeks.]

Clinical Neuroscience

[Radiosurgery of intracerebral cavernomas - Current Hungarian practice]

FEDORCSÁK Imre, NAGY Gábor, DOBAI József Gábor, MEZEY Géza, BOGNÁR László

[Background and purpose - Radiosurgery is an increasingly popular treatment option especially for deep eloquent intracerebral cavernomas that are often too risky for surgical removal, but their re-bleed carries significant risk for persisting neurological deficit. Gamma-radiation based radiosurgery has been being available since 2007 in Hungary in Debrecen. Our aim is to summarize our experience accumulated during the first five years of treatment and to compare it to the international experience. Patient selection and methods - We retrospectively analyzed 51 cavernomas in 45 patients treated between 2008 and 2012 in terms of localization, natural history, and the effect of radiosurgery on re-bleed risk and epilepsy, and its side effects. Results - We treated 26.5% deep eloquent (brainstem, thalamic/basal ganglia) and 72.5% superficial hemispheric cavernomas. The median presentation age was 25 years (13-60) for deep, and 45 years (6-67) for superficial cavernomas. They were treated median of 1 year after presentation. 64.5% of deep cavernomas bled before treatment, the annual risk of first hemorrhage was 2%/lesion, re-bleed risk 21.7%, with 44% persisting morbidity. 13.5% of superficial cavernomas bled prior to treatment, the risk of first bleed was 0.3%, there was no re-bleed, and 35% caused epilepsy. We used GammaART-6000TM rotating gamma system for treatment, marginal dose was 14 Gy (10-16), and treatment volume 1.38-1.53 cm3. Re-bleed risk of deep eloquent lesions fell to 4% during the first two years after treatment and to 0% thereafter, and no hemorrhage occurred from superficial lesions after treatment. Persisting morbidity in deep lesions came from adverse radiation effect in 7% and from re-bleed in 7%, and there was no persisting side effect in superficial cavernomas. 87.5% of cases of epilepsy resistant to medical therapy improved. Radiological regression was found in 37.5% and progression in 2% after treatment. Conclusions - Radiosurgery of cavernomas is safe and effective. Early preventive treatment for deep cavernomas carrying high surgical risk is justified. Moreover, for superficial lesions that are surgically easily accessible radiosurgery also appears to be an attractive alternative.]

Clinical Neuroscience

Mental health of physicians - nationwide representative study from Hungary


Background and aim - Somatic and mental health and stress factors of physicians became an issue of growing interest in both national and international researches. Our aim is to give an overviewing analysis of Hungarian physicians’ mental health state. Methods - Representative, cross-sectional, quantitative survey on a representative sample of Hungarian physicians (n=4784). The control group was formed by the population group of a national survey conducted by “Hungarostudy 2013” (n=2000). Results - Suicidal thoughts (18.8% vs. 9.6%, p<0.001), the scores of Somatic Symptom Scale (PHQ-10, 20.4% vs. 13.6%, p<0.001) were significantly higher among physicians. The suicidal attempts (1.9% vs. 3.5%, p=0.053) and BDI depression scores (7.9% vs. 29.5%, p<0.001) were significantly higher in the control group. High Perceived Stress Scale (PPS) scores occurred in 43.3% of the physicians sample, and 43.4% of them had high scores in the Athenian Insomnia Scale (AIS). The young (<35) female physicians showed significantly higher rates of suicidal thoughts, higher scores of PHQ and PPS. In the young female cohort, the AIS scores were significantly higher than of the other physicians. Conclusions - Mental health of physicians (sleep disorders, suicidal thoughts and psychosomatic symptoms) showed poorer results than the population data. BDI scores and the rate of suicidal attempts showed favourable trends. The next step in the physicians’ mental health researches is to investigate the most decisive risk factors, and to work out the prevention tools.

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Clinical Neuroscience

[Early mental test - developing a screening test for mild cognitive impairment]

KÁLMÁN János, PÁKÁSKI Magdolna, HOFFMANN Ildikó, DRÓTOS Gergely, DARVAS Gyöngyi, BODA Krisztina, BENCSIK Tamás, GYIMESI Alíz, GULYÁS Zsófia, BÁLINT Magdolna, SZATLÓCZKI Gréta, PAPP Edina

[Background and purpose - Mild cognitive impairment (MCI) is a heterogenous syndrome considered as a prodromal state of dementia with clinical importance in the early detection of Alzheimer’s Disease. We are currently developing an MCI screening instrument, the Early Mental Test (EMT) suitable to the needs of primary care physicians. The present study describes the validation process of the 6.2 version of the test. Methods - Only subjects (n=132, female 95, male 37) over the age of 55 (mean age 69.2 years (SD=6.59)) scoring at least 20 points on Mini-Mental State Examination (MMSE), mean education 11.17 years (SD=3.86) were included in the study. The psychometric evaluation consisted of Alzheimer’s Disease Assessment Scale Cognitive subscale (ADAS-Cog) and the 6.2 version of EMT. The statistical analyses were carried out using the 17.00 version of SPSS statistical package. Results - The optimalised cut-off point was found to be 3.45 points with corresponding 69% sensitivity, 69% specificity and 69% accuracy measures. The Cronbach-α, that describes the internal consistence of the test was 0.667, which is higher as compared with the same category in the case of the ADASCog (0.446). A weak negative rank correlation was found between the total score of EMT 6.2 and the age of probands (rs=-0.25, p=0.003). Similarly, only a weak correlation was found between the education levels and the total score of EMT 6.2 (rs=0.31, p<0.001). Two of the subtests, the repeated delayed short-time memory and the letter fluency test with a motorical distraction task had significantly better power to separate MCI and control groups than the other subtests of the EMT. Conclusion - The 6.2 version of EMT is a fast and simple detector of MCI with a similar sensitivity-specificity profile to the MMSE, but this version of the test definitely needs further development.]

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

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

GALARIOTIS Vasilis, BÓDI Nikoletta, JANKA Zoltán, KÁLMÁN János

[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.]

Clinical Neuroscience

[Calcium ion is a common denominator in the pathophysiological processes of amyotrophic lateral sclerosis]

PATAI Roland, NÓGRÁDI Bernát, MESZLÉNYI Valéria, OBÁL Izabella, ENGELHARDT József István, SIKLÓS László

[Amyotrophic lateral sclerosis (ALS), the most frequent motor neuron disease is characterized by progressive muscle weakness caused by the degeneration of the motor neurons in the spinal cord and motor cortex. However, according to the recent observations, ALS is a rather complex syndrome which frequently involves symptoms of cognitive impairment. Therefore, ALS cases can be interpreted in a clinico-pathological spectrum spanning from the classical ALS involving only the motor system to the fronto-temporal dementia. The progression of the disease, however, manifested in the degeneration of the upper and lower motor neurons, is based on the same complex pathobiology. The main elements of the pathomechanism, such as oxidative stress, excitotoxicity, immune/inflammatory processes and mitochondrial dysfunction are well described already, which operate in orchestrated way and amplify the deleterious effect of each other. It is assumed that calcium ions act as a catalyst in this interaction, hence each of the individual mechanisms has strong, positive and reciprocal calcium dependence thus may combine the individual pathological processes into a unified escalating mechanism of neuronal destruction. This review provides an overview of the role of calcium in connecting and amplifying the major mechanisms which lead to degeneration of the motor neurons in ALS. ]

Lege Artis Medicinae



[Atherosclerosis and hypertension are the leading etiological factors in the pathogenesis of cerebral hemorrhage. With old age though, several other factors may appear of which cerebral amyloid angiopathy (CAA) is of major importance. This condition is characterized by the deposition of β-amyloid in the leptomeningeal vessels as well as in the small and medium sized arteries of the cerebral cortex and it is not associated with systemic amyloidosis. This pathological protein is also seen in the brains of otherwise healthy older individuals and may also appear in other diseases such as Alzheimer disease, Down-syndrome, vascular malformations, spongiform encephalopathy and dementia pugilistica. The condition may be asymptomatic but it may also cause cerebral hemorrhage, dementia or various transient neurological symptoms. Most cases are sporadic, but familial subtypes have also been described.]