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

[Earlier and more efficiently: the role of deep brain stimulation for parkinson’s disease preserving the working capabilities]

DELI Gabriella, BALÁS István, KOMOLY Sámuel, DÓCZI Tamás, JANSZKY József, ASCHERMANN Zsuzsanna, NAGY Ferenc, BOSNYÁK Edit, KOVÁCS Norbert

[Background – The recently published “EarlyStim” study demonstrated that deep brain stimulation (DBS) for the treatment of Parkinson’s disease (PD) with early fluctuations is superior to the optimal pharmacological treatment in improving the quality of life and motor symptoms, and preserving sociocultural position. Our retrospective investigation aimed to evaluate if DBS therapy was able to preserve the working capabilities of our patients. Methods – We reviewed the data of 39 young (<60 years-old) PD patients who underwent subthalamic DBS implantation at University of Pécs and had at least two years follow-up. Patients were categorized into two groups based on their working capabilities: Patients with active job (“Job+” group, n=15) and retired patients (without active job, “Job-” group, n=24). Severity of motor symptoms (UPDRS part 3), quality of life (EQ-5D) and presence of active job were evaluated one and two years after the operation. Results – As far as the severity of motor symptoms were concerned, similar (approximately 50%) improvement was achieved in both groups. However, the postoperative quality of life was significantly better in the Job+ group. Majority (12/15, 80%) of Job+ group members were able to preserve their job two years after the operation. However, only a minimal portion (1/24, 4.2%) of the Job- group members was able to return to the world of active employees (p<0.01, McNemar test). Conclusion – Although our retrospective study has several limitations, our results fit well with the conclusions of “EarlyStim” study. Both of them suggest that with optimal timing of DBS implantation we may preserve the working capabilities of our patients.]

Clinical Neuroscience

Vestibular evoked myogenic potential responses in Parkinson’s disease

CICEKLI Esen, TITIZ Pinar Ayse, TITIZ Ali, OZTEKIN Nese, MUJDECI Banu

Background - Our objectives were to determine the differences in the vestibular evoked myogenic potential (VEMP) responses in patients diagnosed with early staged idiopathic Parkinson’s disease (PD) compared to the normal population and evaluate the vestibular system disorder causing balance-posture disorders. Second aim of this study was to investigate caloric test responses particularly in early staged PD compared to normal popu­lation. Material and methods - Thirty patients (14 females and 16 males; mean age, 60.6 ± 13.1 years) diagnosed with idiopathic PD and 28 healthy subjects (20 males and 8 females; mean age, 59.1 ± 6.4 years) were included. The patient and control groups were subdivided according to their age, gender and the patient group was subdivided according to onset time of the Parkinson symptoms, Hoehn-Yahr staging. The subgroups were compared for VEMP and caloric test responses. Results - There were no significant differences between the study and control groups for right and left VEMP measurements. Patients over 60 years and under 60 years did not show significant differences in terms of right and left mean VEMP measurements. However, P1 amplitude was significantly lower in patients over 60 years old (P = .004). Gender, disease duration, BERG balance scale and Hoehn-Yahr stage had no effect on the VEMP amplitudes. There was no significant correlation with the side of Parkinsonian symptoms to the side of canal paresis (P = .566) and the side on which no VEMP response was obtained in caloric test. Conclusion - VEMP responses were not different between PD and healthy subjects. VEMP P1 amplitude was decreased with age in PD group. Canal paresis and symptoms side were not statistically correlated in caloric test.

Clinical Neuroscience

[Recommendation for treatment options in advanced Parkinson's disease]

ASCHERMANN Zsuzsanna, DIBÓ György, KLIVÉNYI Péter, KOVÁCS Norbert, KOVÁCS Tibor, TAKÁTS Annamária, GERTRÚD Tamás, VARANNAI Lajos

[The treatment of advanced Parkinson’s disease is challenging for both physicians and caregivers. The device-aided therapies need expertise and dedicated hospital centers. In this summary we have concluded the available data and recommendation for the treatment options in advanced Parkinson’s disease and adopt them to the daily care in Hungary. ]

Clinical Neuroscience

[UPDATES IN PRACTICAL NEUROLOGY - I. THE PRINCIPLES OF MODERN LEVODOPA THERAPY IN PARKINSON’S DISEASE]

KLIVÉNYI Péter, VÉCSEI László

[Despite the levodopa is used for the treatment of Parkinson’s disease for a long time, recently many questions raised about its clinical use. New issues emerged based on the clinical trials, on latest neuroimaging data and on better understanding the pathomechanism of motor complications. These observations have changed the routine clinical use of levodopa. In this review we summarize the evidences and practical implications of levodopa therapy.]

Clinical Neuroscience

[THE ROLE OF TREMOROMETRY IN PREDICTING THE OUTCOME OF ABLATIVE SURGERIES]

KOVÁCS Norbert, BALÁS István, ILLÉS Zsolt, KELLÉNYI Lóránt, NAGY Ferenc

[Ablative neurosurgical interventions are widely used for the treatment of advanced Parkinson's disease. However, in some cases, the achieved result is temporary and repeat operation is necessary to obtain a permanent effect. By analyzing 30 ablative surgeries using comparative accelerometry, we looked for a biological marker predicting the efficiency. In 27 cases where clinical symptoms were permanently improved, a significant increase in rest tremor frequency was observed in addition to reduction in tremor intensity. In contrast, in those three cases where the clinical effect of the surgery was only temporary, the frequency of tremor remained unchanged despite of the transitory decrease in intensity. We thus hypothesize that postoperative change in frequency of tremor but not the intensity may predict the outcome of ablative treatments.]