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Clinical Neuroscience

NOVEMBER 30, 2019

[The applicability of 123I-FP-CIT SPECT dopamine transporter imaging in clinical practice]

PERLAKI Gábor, SZEKERES Sarolta, JANSZKY József, DEZSŐ Dániel, ASCHERMANN Zsuzsanna, ZÁMBÓ Katalin, KOVÁCS Norbert

[The 123I-FP-CIT dopamine transporter SPECT imaging is a sensitive method to assess functional dopaminergic neuron terminals in the striatum. The method has also been available in Hungary for years. There are two main indications: (i) to help differentiate essential tremor from clinically uncertain Parkinsonism, including patients with early symptoms and (ii) to help differentiate dementia with Lewy bodies from Alzheimer’s disease. The aim of this paper is to review 123I-FP-CIT SPECT imaging based on international data/guidelines and our own experiences, thereby assisting nuclear medicine practitioners and neurologists.]

Clinical Neuroscience

MAY 30, 2019

[Dopamine agonists in Parkinson’s disease therapy - 15 years of experience of the Neurological Clinics from Tîrgu Mureș. A cross-sectional study ]

SZÁSZ József Attila, CONSTANTIN Viorelia, MIHÁLY István, BIRÓ István, PÉTER Csongor, ORBÁN-KIS Károly, SZATMÁRI Szabolcs

[Background and purpose - There is relatively few data regarding the usage of dopaminagonists for the treatment of Parkinson’s disease; furthermore, there are no publications regarding Central- and Eastern-European countries. The aim of the study was to evaluate the use of dopamine agonists as a therapeutic option amongst Parkinson’s disease patients admitted to the Neurological Clinics of Tîrgu Mures during the last 15 years. Methods - In our study we investigated the data of all Parkinson’s patients treated at our clinics between the 1st of January 2003 and the 31st of December 2017. We analyzed the particularities of dopamine agonists’ usage based on the therapeutic recommendations from the final report of these patients. Regarding time since the diagnosis, we divided the patients in two groups: less than or equal to 5 years and more than 5 years. Results - During the studied period a total of 2379 patients with Parkinson’s disease were treated at the Clinics. From the 1237 patients with disease duration under 5 years 665 received dopamine agonists: 120 as monotherapy, 83 together with monoamine oxidase inhibitors and in 234 cases associated with levodopa. The remaining 228 patients were treated with a triple combination of levodopa, dopamine agonists and monoamine oxidase inhibitors. In patients suffering from Parkinson’s disease for more than 5 years, in 364 cases out of 653 a dopamine agonist was part of the therapy. Conclusion - The usage of dopamine agonists was similar to the data presented in other studies. We consider that clinicians treating the disease should, with the necessary prudence, use the available and recommended dopamine agonist with the utmost courage to their maximum therapeutic potential.]

Clinical Neuroscience

JANUARY 30, 2018

Insights into the structure and function of the hippocampal formation: Relevance to Parkinson’s disease

GYÖRFI Orsolya, NAGY Helga, BOKOR Magdolna, KÉRI Szabolcs

The link between the hippocampus and declarative memory dysfunctions following the removal of the medial temporal lobe opened unexplored fields in neuroscience. In the first part of our review, we summarized current theoretical frameworks discussing the role of hippocampus in learning and memory. Several theories are highlighted suggesting that the hippocampus is responsible for assembling stimulus elements into a unitary representation that later can be utilized to simulate future events. The hippocampal formation has been implicated in a growing number of disorders, from neurodegenerative diseases to atypical cognitive ageing and depression. Recent neuroimaging studies provided new opportunities to study in detail the hippocampal formation’s role in higher levels of the nervous system. We will present data regarding the regional specialization of the hippocampus in experimental models developed for healthy and neurological conditions with a special focus on Parkinson’s disease. Combined evidence from neuroimaging studies suggested that hippocampal volume is reduced in non-demented, newly diagnosed patients with Parkinson’s disease, which is associated with impaired memory performance. These findings proposed that, beyond the well-known striatal dopamine loss, impaired hippocampal synaptic plasticity may contribute to cognitive and affective impairments in early Parkinson’s disease.

Lege Artis Medicinae

DECEMBER 20, 2014

[The complexity of hyper-lipidaemia’s follow-up in a polymorbid patient diagnosed with newfound Parkinson’s disease]

HANG Dóra

[The 73-year-old polymorbid man has been examined because of above normal blood pressure and increased serum lipid levels. From his already known diseases subclinic hypothyreosis should be highlighted. Because of increased serum cholesterol (6.7 mmol/l) and LDL levels (4.91 mmol/l) 40 mg atorvastatin has been adjusted besides 10 mg amlodipine against his high blood pressure. Subsequently selegiline and levodopa/benserazid therapy have been adjusted caused by newly diagnosed Parkinson’s disease. Parallel in time decreased dosage of atorvastatin (20 milli- gramms) has been enabled to adjust as well, the pill taken by the patient is combinated with 10 milligramms of amlodipine and called Amlator®. The improvement of lipid levels might be due to the trasformation of subclinic hypothyroidism to euthyroid state of the thyroid gland. Levodopa might plays role in this improvement resulting in an inhibition of TSH release because of demonstrated dopamine-receptors in the pituitary gland.]

LAM Extra for General Practicioners

JUNE 10, 2014

[The possibilities of pharmacological treatment of obesity]

PADOS Gyula, SIMONYI Gábor, BEDROS J. Róbert

[There have been attempts to treat obesity with medicines for nearly 100 years, since the discovery of ephedrine. For decades amphetamine derivates and agents stimulating or inhibiting the release of noradrenaline and dopamine have been applied. However, most of theses drugs had to be gradually withdrawn, due to their adverse effects on the cardiovascular and central nervous system or their sympaticotonic effect. Dexfenfluramine (Isolipan), which was introduced in the 90s, did not have such side effects, but it turned out to potentially cause valvular heart disease. Finally, sibutramin (Reductil) was introduced, which again had to be withdrawn in 2010 due to its hypertensive and cardiovascular side effects. After all, we were left without any appetite-suppressant drugs. Orlistat therapy, (Xenical 120 mg, alli 60 mg - OTC), which inhibits the absorption of fat, can eliminate only 30% of the consumed food's fat content, at the price of gastrointestinal side effects. The latest result of research carried out wordwide is that in 2012 the FDA approved commercial distribution of the selective 5HT2/c serotonin agonist lorcaserin (Belviq), which enhances satiety, in the USA. Unfortunately, in 2013 the EMEA temporarily postponed the lauch of this drug, until certain adverse effects are excluded. For diabetic patients, the GLP-1 agonist exenatid and the GLP-analog liraglutid, which can also reduce body weight, are available in the form of injections. ]

Lege Artis Medicinae

DECEMBER 18, 2013

[The possibilities of pharmacological treatment of obesity]

PADOS Gyula, SIMONYI Gábor, BEDROS J. Róbert

[There have been attempts to treat obesity with medicines for nearly 100 years, since the discovery of ephedrine. For decades amphetamine derivates and agents stimulating or inhibiting the release of noradrenaline and dopamine have been applied. However, most of theses drugs had to be gradually withdrawn, due to their adverse effects on the cardiovascular and central nervous system or their sympaticotonic effect. Dexfenfluramine (Isolipan), which was introduced in the 90s, did not have such side effects, but it turned out to potentially cause valvular heart disease. Finally, sibutramin (Reductil) was introduced, which again had to be withdrawn in 2010 due to its hypertensive and cardiovascular side effects. After all, we were left without any appetite-suppressant drugs. Orlistat therapy, (Xenical 120 mg, alli 60 mg - OTC), which inhibits the absorption of fat, can eliminate only 30% of the consumed food’s fat content, at the price of gastrointestinal side effects. The latest result of research carried out wordwide is that in 2012 the FDA approved commercial distribution of the selective 5HT2/c serotonin agonist lorcaserin (Belviq), which enhances satiety, in the USA. Unfortunately, in 2013 the EMEA temporarily postponed the lauch of this drug, until certain adverse effects are excluded. For diabetic patients, the GLP-1 agonist exenatid and the GLP-analog liraglutid, which can also reduce body weight, are available in the form of injections.]

Clinical Neuroscience

NOVEMBER 30, 2013

[Assessment of the role of multidrug resistance-associated proteins in MPTP neurotoxicity in mice]

PLANGÁR Imola, ZÁDORI Dénes, SZALÁRDY Levente, VÉCSEI László, KLIVÉNYI Péter

[Goals - The available scientific data indicate that the pathomechanism of Parkinson's disease (PD) involves the accumulation of endogenous and exogenous toxic substances. The disruption of the proper functioning of certain transporters in the blood-brain barrier and in the blood-cerebrospinal fluid barrier in PD would accompany to that accumulation. Although there is an emerging role of the dysfunction of multidrug resistance-associated proteins (MRPs), members of ATP-binding cassette (ABC) transporter superfamily, in neurodegenerative disorders, there is only a few available data as regards PD. So the aim of our study was the assessment of the role of certain MRPs (1,2,4 and 5) in neurotoxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Methods - Following the intraperitoneal administration of silymarin (with MRP1, 2, 4 and 5 inhibitory effects), naringenin (with MRP1, 2 and 4 stimulatory effects), sulfinpyrazone (with MRP1, 4 and 5 inhibitory and MRP2 stimulatory effects) and allopurinol (with MRP4 stimulatory effect) in doses of 100 mg/kg, 100 mg/kg, 100 mg/kg and 60 mg/kg, respectively, for one week before and after the administration of MPTP in C57B/6 mice in acute dosing regimen, the striatal concentrations of dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid has been measured using high-performance liquid chromatography. Results - Although the results of these experiments showed that neither of these substances exerted significant influence on MPTP-induced striatal depletion of dopamine and its metabolites, naringenin exerted a slight prevention of dopamine decrease, while allopurinol considerably enhanced the MPTP-induced lethality in mice. The explanation of these findings would be that the stimulation of MRP1- and MRP2-mediated transport of glutathione conjugates of toxic substances may have slight beneficial effects, while stimulation of MRP4-mediated efflux of brain urate, which has an important antioxidant potency, may worsen the effects of oxidative stress.]

Clinical Neuroscience

NOVEMBER 30, 2011

[Vascular or “lower body parkinsonism”. Rise and fall of one diagnosis]

SZIRMAI Imre

[The “arteriosclerotic parkinsonism”, which is called vascular parkinsonism (VP), was first described by Critchley1. The broad based slow gait, reduced stride lenght, start hesitation, freezing and paratonia was mentioned as “lower body parkinsonism” (LBP) which can be associated by slow speech, dysexecutive syndrome, and hand tremor of predominantly postural character. In VP the DAT-scan proved normal dopamine content of the striatum in contrast with Parkinson’s disease (PD). Additionally, Lewy bodies of brainstem type were not found in VP. Probability of VP increases if central type pathologic gait is prominent; the hands are slightly involved, the MRI indicates transparent periventricular white substance and/or brain atrophy. In some cases differentiation of gait apraxia and parkinsonism could be challenging. There is no rigor of the lower limbs at rest in neither of them, the disturbance of movement is evoked by the gait itself. Three subtypes of “gait ignition failure” has been recently described: (1) ignition apraxia, (2) equilibrium apraxia and (3) mixed gait apraxia. The primary progressive freesing gait was considered as a Parkinson-plus syndrome. Freesing occurs more frequently in diseases with pakinsonism than in PD. The grade of ventricle dilatation and the frontal leukoaraiosis was similar in LBP and gait apraxia. In cases of normal pressure hydrocephalus the impaired gait may mimic PD. Pathologic gait in VP can be explained by the lesions of the senso-motor association pathways in dorsal paramedian white substance within the vulnerable borderzone region. These may be colocalized with the representation of the lower extremities in the posterior third of the supplementer motor area. Rektor2 proposed to change the name of LBP to “cerebrovascular gait disorder”. Notwithstandig central type gait disorder develops also in many degenerative diseases other than cerebro-vascular origin. The neuronal net controling the regulation of movement is widespread, therefore several cortical and subcortical lesions could elicit large variations of pathologic gait, ie.: ataxia, apraxia, ignition failure, akinesis etc. In conclusion: most of the central gait disorders regarding the pathology and their appearance can not be called “parkinsonism”; these are much closer related to the localization of lesions rather than to the diagnostic categories.]

Clinical Neuroscience

AUGUST 20, 2002

[Parkinson's syndrome and cognitive disorders]

SZIRMAI Imre, KOVÁCS Tibor

[The cognitive (executive) ability of patients with Parkinson’s-disease (PD) deteriorates gradually during the progression of the disease. Fluency of speech, word finding, working memory, ability to plan the future and flexibility decline. Cognitive disturbance was found to be proportional with the speech, posture, gait and balance problems and can not be influenced by L-dopa substitution. Apart the dorsal and ventral mesolimbic dopaminergic systems the coerulo-cortical noradrenergic, serotoninergic and cholinergic systems are also impaired in PD. Subcortical dementia in PD can also be explained by the functional dysability of dorsolateral and anterior cingular circuits. Attention deficit can be explained by the dopamine depletion of cingular cortex. Cortical Lewy bodies, neurofibrillary tangles, neurit plaques and additional vascular pathology should also play a role in cognitive impairment of PD. In several systemic degenerative diseases associating with Parkinson’s syndrome (PS) ie. progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), multiple system atrophy (MSA) dementia can be detected with various severity, therefore the question arises concerning the correlation between cognitive disability and PS. Parkinson syndrome can also develop in frontotemporal dementias (FTD), Alzheimer’s disease and cortical Lewy body disease (CLBD) but no correlation exists between motor disability and severity of dementia. In CLBD dementia can be the initial symptom in 18% of cases but PS can also preceedes the dementia. In PSP profound depletion of other monoaminergic neurotransmitter system was also reported. In FTDs associated with PS degeneration of substantia nigra, locus coeruleus and basal nucleus of Meynert has been reported with increased number of neurofibrillary tangles. In patients with vascular PS (VP) there is generally no tremor and rigidity, but pseudobulbar palsy, dementia, gate disturbance, incontinency appeares; L-dopa treatment is generally ineffective. In VP no cellular loss can be found within the substantia nigra, but leukoaraiosis, lacunae in the white matter and basal ganglia are commonly demonstrated.]

Clinical Neuroscience

JANUARY 20, 2007

[PRAMIPEXOLE THERAPY OF RESTLESS LEGS SYNDROME]

VIDA Zsuzsanna, SZAKÁCS ZOLTÁN

[The restless legs syndrome is a disorder belonging to the family of movement disorders during sleep, often remains unrecognized, although it is the second most common cause of chronic sleep deficiency and daytime sleepiness. In accordance with international guidelines, pharmacotherapy of this disorder should begin with a dopamine agonist. Owing to their efficacy and favorable safety profile, newly introduced, selective dopamine agonists have become extensively used for this purpose. This study evaluated the efficacy of one of the products in this group, pramipexole. Fifty-one patients suffering from idiopathic restless legs syndrome underwent monotherapy with pramipexole in daily doses of 0.25 to 1.0 mg. Therapeutic efficacy was evaluated using three tools, i.e. follow-up questionnaires, actigraphy, and Forced Immobilisation Test. An excellent therapeutic effect was seen in more than 80 per cent of the study population. As shown by findings of the follow-up questionnaires, pramipexole resulted in substantial improvements of both daytime and nighttime symptoms of RLS. Actigraphy monitoring demonstrated a statistically significant increase in the ratio of time spent without limb movement to the time spent in bed; furthermore, the result of the Forced Immobilisation Test also improved. It seems fair to conclude from the findings of this study that pramipexole monotherapy is an effective treatment in restless legs syndrome.]