Clinical Neuroscience

[Clinical studies on pramipexol retard]

KLIVÉNYI Péter, VÉCSEI László

MAY 30, 2010

Clinical Neuroscience - 2010;63(05-06)

[Pramipexol retard is the newest drug for the treatment of Parkinson’s disease. The prolonged release of the agent in this preparation allows a more continuous dopaminergic stimulation than previous preparations, without reducing the agent’s already known and proven clinical efficiency. In addition, it has a more favourable adverse effect profile than previous preparations, and patient compliance can also be better as it needs to be taken only once daily. These benefits have been proven in recent clinical studies, of which the most important ones are reviewed here.]

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Clinical Neuroscience

[Neurology! Adieau? (Part 1)]

SZIRMAI Imre

[The neurological practice suffered considerable changes during the last twenty years. The recent therapeutic methods and the acceptance of the ideology of evidence based medicine, which is based on confidence in statistics, changed the reasoning of the neurologists. Therapy protocols intrude into the field of individual medicine, and doctors accept treatment schemes to alleviate responsibility of their decisions. In contrast with this, recent achievements in pharmacogenetics emphasize the importance of individual drug therapies. The protocol of intravenous cerebral thrombolysis does not require defining the origin of cerebral ischaemia in the acute stage, therefore, this procedure can be regarded as human experiment. According to the strict protocol thrombolysis might be indicated only in 1-8% of patients with cerebral ischaemia. According to the Cohrane database more trials are needed to clarify which patients are most likely to benefit from treatment. Because of the change in therapeutic principles transient ischaemic attack has been newly defined as “acute neurovascular syndrome”. Multiplication of neurological subspecialties has been facilitated by the development of diagnostic tools and the discovery of effective new drugs. The specialization led to narrowing of interest and competency of clinicians. Several new neurological scientific societies were founded for the representation of specific disorders. In Hungary, between 1993 and 2000 nine scientific societies were grounded within the field of clinical neurology. These societies should be thankful to the pharmaceutical industries for their existence. In some European countries in 2007 only three neurological subspecialties were accepted, which are neurophysiology, neuro-rehabilitation and childneurology. Neuro-radiology is in the hands of general radiologists, the specialization is not granted for neurologists. Because of the subspecialization the general professionalism of neurologists has diminished. Among young neurologists the propedeutic skills suffered most seriously. Subspecialisation of teachers also interferes with the practice oriented teaching of medical students and residents.]

Clinical Neuroscience

[Neurology! Adieau? (Part 2)]

SZIRMAI Imre

[Teaching of neurologists is indisposed worldwide. University tutors are engaged in teaching, research and patient-care. This triple challenge is very demanding, and results in permanent insecurity of University employees. To compensate for the insufficient clinical training, some institutes in the USA employ academic staff members exclusively for teaching. The formation of new subspecialties hinders the education and training of general neurologists. At the present four generations of medical doctors are working together in the hospitals. The two older generations educate the younger neurologists who have been brought up in the world of limitless network of sterile information. Therefore their manual skills at the bedside and knowledge regarding emergency treatment are deficient. Demographics of medical doctors changed drastically. Twice as many women are working in neurology and psychiatry than men. Integrity of neurology is threatened by: 1. Separation of the cerebrovascular diseases from general neurology. Development of "stroke units" was facilitated by the better reimbursement for treatment and the interest of the pharmaceutical companies. The healthcare politics assisted to split the neurology into two parts. The independent status of “stroke departments” will reduce the rest of clinical neurology to outpatient service. 2. The main argumentation to segregate the rare neurological diseases was that their research will provide benefit for the diseases with high prevalence. This argumentation can rather be considered territorial imperative. The separation of rare diseases interferes with the teaching of differential diagnostics during neurological training. The traditional pragmatic neurology can not be retrieved. The faculty of neurology could retain its integrity because of the improvement of diagnostic methods and the more and more effective drugs. Nevertheless, even the progression of neurological sciences induces dissociation of clinical neurology. Neurology shall suffer fragmentation if the professional authorities fail to control the separation of subspecialties, if teaching of future neurologists, including practical knowledge and skills of diagnostic decision making, is not supported.]

Clinical Neuroscience

[Image fusion guided brachytherapy of brain tumors]

JULOW Jenő

[The paper is the summary of mostly published works of the clinical results of intracavitary Yttrium-90 colloid irradiation of recurrent cystic craniopharyngiomas, and Iodine-125 interstitial irradiation of gliomas, pinealomas, brainstem tumors, recurrent meningeomas, solid craniopharyngiomas and metastases. It concisely demonstrates the usefulness of image fusion in the verification of isotope seeds and catheters, the comparison of 125 Iodine stereotactic brachytherapy and LINAC radiosurgery modalities on physical dose distribution and radiobiological efficacy, and the analysis of volumetric changes after interstitial irradiation of gliomas. Results of the immunohistochemical study deal with the role of microglia/macrophage system in the tissue response to I- 125 interstitial brachytherapy of cerebral gliomas. Due to financial reasons, gamma knife and Linac are not available to many countries and neurosurgical institutes. In the absence of the above mentioned radiosurgical methods, we have shown brachytherapy as an alternative solution in the treatment of different types of inoperable or recurrent brain tumors. The observed results may be noticable at LINAC and gamma knife irradiation too.]

Clinical Neuroscience

[Epidemiology of dementia in Hungary]

ÉRSEK Katalin, KÁRPÁTI Krisztián, KOVÁCS Tibor, CSILLIK Gabriella, GULÁCSI L. Ádám, GULÁCSI László

[Objective - To estimate the epidemiology and the distribution of disease severity of dementia in Hungary, using published data. To estimate the demented population of 2008 and to make a projection for 2050. Methodology - With an outlook for the international professional literature and the available Hungarian information we examine the epidemiology of dementia in Hungary by age-groups and disease severity (according to MMSE categories), then make our estimation for the entire population. Results - Based on the estimation of the number of demented people in Hungary there is a noticeable difference between the domestic and the internationally published data. According to previous Hungarian studies, the number of the demented subjects vary between 530 and 917 thousand patients. Multiplying the elderly age-group’s populations by the global prevalence data it results in 101 thousand of demented patients. Estimation by the domestic published data we remarkably overestimate the presumed value, whereas by using the global prevalence figures we underestimate. Conclusions - There is a strong need for a representative study to obtain exact figures on the prevalence of dementia in Hungary. Getting exact figures of the Hungarian prevalence of dementia it is a strong need an overall representative study. With the lack of it the health and social care systems are not able to prepare for providing the increasing number of patients.]

Clinical Neuroscience

[Antinociceptive effect of vinpocetine - a comprehensive survey]

CSILLIK Bertalan, MIHÁLY András, KNYIHÁR-CSILLIK Elizabeth

[Blockade of retrograde transport of nerve growth factor (NGF) in a peripheral sensory nerve is known to induce transganglionic degenerative atrophy (TDA) of central sensory terminals in the upper dorsal horn of the related, ipsilateral segments(s) of the spinal cord. The ensuing temporary blockade of transmission of nociceptive impulses has been utilized in the therapy of intractable pain, using transcutaneous iontophoresis of the microtubule inhibitors vincristin and vinblastin, drugs which inhibit retrograde transport of NGF. Since microtubule inhibition might inhibit (at least theoretically) mitotic processes in general, we sought to find a drug which inhibits retrograde transport of NGF without microtubule inhibition. Vinpocetine, a derivate of vincamine, which does not interfere with microtubular function, was found to inhibit retrograde axoplasmic transport of NGF in peripheral sensory nerves, similarly to vincristin and vinblastin. Blockade of NGF transport is followed by transganglionic degenerative atrophy in the segmentally related, ipsilateral superficial spinal dorsal horn, characterized by depletion of the marker enzymes of nociception, fluoride resistant acid phosphatase (FRAP) and thiamine monophosphatase (TMP) from the Rolando substance and by decrease of the pain-related neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) from lamina I-II-III. Based upon these findings, it has been suggested that vinpocetine may result in a locally restricted decrease of nociception. Herewith, the structural and behavioral effects of perineurally administered vinpocetine are discussed. Nociception, induced by intraplantar injection of formalin, was mitigated by perineural application of vinpocetine; also formalin-induced expression of c-fos in the ipsilateral, segmentally related superficial dorsal horn, was prevented by this treatment. Since vinpocetine is not a microtubule inhibitor, its mode of action is enigmatic. It is assumed that the effect of vinpocetine might be related to interaction with membrane-trafficking proteins, such as signalling endosomes and the endocytosis-mediating „pincher” protein, involved in retrograde axoplasmic transport of NGF, or to interaction with glial elements, recently reported to be involved in the modulation of pain in the spinal cord. Based on animal experiments it is assumed that the temporary, locally restricted decrease of nociception, induced by vinpocetine applied via transcutaneous iontophoresis, might open up new avenues in the clinical treatment of intractable pain.]

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Clinical Neuroscience

Comparison of pramipexole versus ropinirole in the treatment of Parkinson’s disease

GENCLER Onur Serdar , OZTEKIN Nese , OZTEKIN Fevzi Mehmet

Parkinson’s disease is a progressive neurodegenerative disease characterized by motor and non-motor symptoms. Levodopa is the most effective drug in the symptomatic treatment of the disease. Dopamine receptor agonists provide sustained dopamin-ergic stimulation and have been found to delay the initiation of levodopa treatment and reduce the frequency of various motor complications due to the long-term use of levodopa. The primary aim of this study was to compare the efficacy of potent nonergoline dopamine agonists pramipexole and ropinirole in both “dopamine agonist monotherapy group” and “levodopa add-on therapy group” in Parkinson’s disease. The secondary aims were to evaluate the effects of these agents on depression and the safety of pramipexole and ropinirole. A total of 44 patients aged between 36 and 80 years who were presented to the neurology clinic at Ministry of Health Diskapi Yildirim Beyazit Training and Research Hospital, Ankara, Turkey and were diagnosed with idiopathic Parkinson’s disease, were included into this randomized parallel-group clinical study. Dopamine agonist monotherapy and levodopa add-on therapy patients were randomized into two groups to receive either pramipexole or ropinirole. The maximum daily dosages of pramipexole and ropinirole were 4.5 mg and 24 mg respectively. Patients were followed for 6 months and changes on Unified Parkinson’s Disease Rating Scale, Clinical Global Impression-severity of illness, Clinical Global Impression-improvement, Beck Depression Inven­tory scores, and additionally in advanced stages, changes in levodopa dosages were evaluated. Drug associated side effects were noted and compared. In dopamine agonist monotherapy group all of the subsections and total scores of Unified Parkinson’s Disease Rating Scale and Clinical Global Impression-severity of illness of the pramipexole subgroup showed significant improvement particularly at the end of the sixth month. In the pramipexole subgroup of levodopa add-on therapy group, there were significant improvements on Clinical Global Impression-severity of illness and Beck Depression Inventory scores, but we found significant improvement on Clinical Global Impression-severity of illness score at the end of the sixth month in ropinirole subgroup too. The efficacy of pramipexole and ropinirole as antiparkinsonian drugs for monotherapy and levodopa add-on therapy in Parkinson’s disease and their effects on motor complications when used with levodopa treatment for add-on therapy have been demonstrated in several previous studies. This study supports the effectiveness and safety of pramipexole and ropinirole in the monotherapy and levodopa add-on therapy in the treatment of Parkinson’s disease.

Clinical Neuroscience

Uric acid: The role in the pathophysiology and the prediction in the diagnosis of Parkinson’s disease: A Turkish-based study

ARI Cagla Buse , TUR Kobak Esma , DOMAC Mayda Fusun , KENANGIL Ozgen Gulay

Oxidative stress has been associated as an essential contributor to the development of neurodegenerative diseases. Recent developments in the field of Parkinson’s Disease (PD) pathophysiology have led to a renewed interest in this field. As an antioxidant, uric acid (UA) has arisen as a potential neuroprotectant. Higher concentrations of UA are linked to reducing the risk of the development of the disease and preventing its progression. However, the expositions are unsatisfactory because the outcomes of these reports have not been consistent. This study is set out to assess the association of whether lower UA concentrations increased the PD risk by investigating its relationship with patients’ demographic and clinical data, and to determine whether previous studies are compatible with the Turkish-sampled population. Furthermore, we aimed to determine UA’s probability of being an early-stage diagnostic marker. A total of 305 patients and 100 healthy controls were included. Serum UA levels of patients and controls were compared with clinical features. We classified the patients into three motor subtypes and determined the disease severity by modified Hoehn&Yahr Staging Scale (mH&Y) and Unified Parkinson’s Disease Rating Scale (UPDRS). Standardized Mini-Mental State Examination (MMSE-TR) was assessed for cognition. There were not any significant differences of age and sex between patients and controls (p=0.030, p=0.132). The mean UA was 5.06±1.33 mg/dL in patients and 5.46±1.44 in controls, and a statistical significance was detected (p=0.022). The mean MMSE-TR were 24.83±4.35 in patients and 27.09±2.13 in controls, and statictical significance was revealed (p=0.001). The mean duration of the disease was 6.31±4.16 years, mean UPDRS scores were 59.74±22.33, and mH&Y scores were 2.29±0.91. In binary comparisons, patients with tremor-dominant motor subtype had lower UA concentrations than controls (p=0.014). ROC curve analysis revealed UA’s cut-off as ≤9.15, the specificity was 99.3, the sensitivity was 10.0, and the area under the curve was 0.576 (p<0.005). Regression analysis revealed age as an independent risk factor on UA values. Oxidative stress might be a factor in the development of PD, and UA may be a possible prospective protecting factor in the clinical course of the disease. However, it does not affect the severity. Our results support that lower uric acid concentrations are associated with PD; however, it is not a powerful indicator for predicting PD risk. As we reveal more about UA and its effect in further investigations, its significant role will become well-defined.

Clinical Neuroscience

Retinal morphological changes during the two years of follow-up in Parkinson’s disease

ATUM Mahmut, DEMIRYÜREK Enes Bekir

The study aims to investigate the relationship between the progression of idiopathic Parkinson’s disease (IPD) and retinal morphology. The study was carried out with 23 patients diagnosed with early-stage IPD (phases 1 and 2 of the Hoehn and Yahr scale) and 30 age-matched healthy controls. All patients were followed up at least two years, with 6-month intervals (initial, 6th month, 12th month, 18th month, and 24th month), and detailed neurological and ophthalmic examinations were performed at each follow-up. Unified Parkinson’s Disease Rating Scale part III (UPDRS Part III) scores, Hoehn and Yahr (H&Y) scores, best-corrected visual acuity (BCVA), intraocular pressure (IOP) measurement, central macular thickness (CMT) and retinal nerve fiber layer (RNFL) thickness were analyzed at each visit. The average age of the IPD and control groups was 43.96 ± 4.88 years, 44.53 ± 0.83 years, respectively. The mean duration of the disease in the IPD group was 7.48 ± 5.10 months at the start of the study (range 0-16). There was no statistically significant difference in BCVA and IOP values between the two groups during the two-year follow-up period (p> 0.05, p> 0.05, respectively). Average and superior quadrant RNFL thicknesses were statistically different between the two groups at 24 months and there was no significant difference between other visits (p=0.025, p=0.034, p> 0.05, respectively). There was no statistically significant difference in CMT between the two groups during the follow-up period (p> 0.05). Average and superior quadrant RNFL thicknesses were significantly thinning with the progression of IPD.

Lege Artis Medicinae

[COVID-19 and Parkinson’s disease]

TÓTH Adrián, TAKÁTS Annamária

[Parkinson’s disease is the elderly people’s condition which increases the risk of infections in the upper airways in its ad­vanced stages. Specific diseases (as hypertension, diabetes mellitus), older age and the male sex are significantly worsening the course of COVID-19. It would be challenging to examine parallel these diseases, since they are raising two important ques­tions. First, if Parkinson’s disease be a risk factor of COVID-19 morbidity and mortality. Se­condly, how the COVID-19 pandemic can influence the Parkinson’s disease patients. The authors are seeking answers to these questions based on the published results in the topic concerned.]

Clinical Neuroscience

[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.]