Clinical Neuroscience

[Strategies of using the new antiepileptic drugs for epilepsy in adults]

NIKL János

JULY 30, 2018

Clinical Neuroscience - 2018;71(07-08)

DOI: https://doi.org/10.18071/isz.71.0249

[The new antiepileptic drugs have not changed the basic pharmacological treatment principles of epilepsy, but they have given greater choice in focal and in generalized epilepsies as well. The new drugs are not necessarily more effective than traditional drugs, but they have favourable pharmacokinetic characteristics, fewer interactions and better adverse effect profile in the acute and chronic phase of the treatment. They generally show a lower teratogenicity risk than the standard antiepileptics, although carbamazepine, one of the standard drugs can be used and zonisamide, a new one must be avoid in pregnancy. Due to characteristics mentioned above they are not only effective as add-on therapy, but in monotherapy as well. On the basis of the international and national recommendation lamotrigine and levetiracetam belong to the first line antiepileptics. The favourable tolerability of the new antiepileptics may improve the patient’s compliance and adherence to the given treatment. The low teratogenicity makes them especially suitable for the treatment of women of childbearing age. The new antiepileptic drugs can succesfully used for the treatment of special patients’ groups as for the post stroke, poszttraumatic epilepsies, for the epilepsies accompanied with brain tumours as well as for epilepsies in the elderly. The new drugs are advantageous for the treatment of such patients who have psychiatric symptoms or signs of cognitive decline and high risk of these symptoms respectively.]

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Clinical Neuroscience

Novel structured MRI reporting system in neonatal hypoxic-ischemic encephalopathy - issues of development and first use experiences

LAKATOS Andrea, KOLOSSVÁRY Márton, SZABÓ Miklós, JERMENDY Ágnes, BAGYURA Zsolt, BARSI Péter, RUDAS Gábor, KOZÁK R. Lajos

Purpose - To develop an evidence-based, standardized structured reporting (SR) method for brain MRI examinations in neonatal hypoxic-ischemic encephalopathy (HIE) suitable both for clinical and research use. Materials and methods - SR template development was based on comprehensive review of the pertinent literature with the basic sections and subdivisions of the template defined according to MRI sequences (both conventional and diffusion-weighted, MR-spectroscopy (MRS), and T2*-weighted imaging), and the items targeted on age-related imaging patterns of HIE. In order to evaluate the usability of the proposed SR template we compared data obtained from the brain MR image analysis of 87 term and 19 preterm neonates with the literature. The enrolled 106 infants were born between 2013 and 2015, went through therapeutic hypothermia according to the TOBY criteria due to moderate to severe asphyxia and had at least one brain MRI examination within the first two weeks of life. Ethical approval was obtained for this retrospective study. Descriptive statistical analysis was also performed on data exported from the structured reporting system as feasibility test. Results - The mean gestational age of the study population was 38.3±2.2 weeks; brain MRI was performed on 5.8±2.9 day of life, hence in 78% of our patients after the conclusion of therapeutic hypothermia. Our main imaging findings were concordant to the pertinent literature. Moreover, we identified a characteristic temporal evolution of diffusion changes. Interestingly 18% (n=19/106) of the clinically asphyxiated infants had isolated axial-extraaxial haemorrhage without any imaging sign of HIE. Conclusion - In this article our approach of reporting HIE cases with our novel SR template is described. The SR template was found suitable for reporting HIE cases, moreover it uncovered time and location dependent evolution of diffusion abnormalities (and pseudonormalization, as well), suggesting its usefulness in clinical research applications. The high number of isolated intracranial haemorrhages, and the changing diffusion pattern emphasizes the importance of early imaging in HIE.

Clinical Neuroscience

[Paradigm shift in management of patients with vertigo and imbalance]

MIKE Andrea, TAMÁS T. László

[Dizziness is one of the most common causes of medical visits. Management of the dizzy patient may be challenging both for the general practitioner, in emergency departments, and special clinics, as behind a seemingly homogeneous clinical presentation several very different etiologies may occur. Research of the last two century enriched our knowledge about physiology and pathophysiology of the vestibular system. Much knowledge is now available about the labyrinth being able to sense head motions and gravity, processing of afferent vestibular stimuli, reflectory oculomotor and postural control, or recovery of the vestibular system. Based on scientific results new beside tests have been introduced including provocation maneuvers for detecting ectopic otoliths in different semicircular canals, head impulse test to examine function of the vestibulo-ocular reflex, and the HINTS+ battery for differentiation of peripheral or central origin of an acute vestibular syndrome. Technical innovations like videooculography and vestibular evoked myogenic potentials enable us to selectively and side-specifically examine the function of all six semicircular canals and two otolith organs. Pathomechanism of disorders with vertigo and dizziness became more clear resulting in the development or amendment of diagnostic criteria of several vestibular disorders including vestibular migraine, Menière’s disease, benign paroxysmal positional vertigo, persistent postural-perceptual dizziness, bilateral vestibulopathy. Broader knowledge about the pathomechanism promoted the development of new therapeutic methods like different repositioning maneuvers in benign paroxysmal positional vertigo, pharmaceutical therapies, vestibular rehabilitation, and psychotherapy. We aimed to summarize the novelties in the field of oto-neurology.]

Clinical Neuroscience

Isocitrate dehydrogenase mutations in defining the biology of and supporting clinical decision making in glioblastoma

KÁLOVITS Ferenc, TOMPA Márton, NAGY Ádám, BERNADETTE Kalman

Background and purpose - Oncogenesis is related to a sequential accumulation of somatic mutations. Comprehensive characterizations of the genomic landscapes have been completed recently for several tumors, glioblastoma being among the first ones. Our own translational research studies have been focused on defining molecular subtypes of glioblastoma in the clinical setting because of an expected prognostic and therapeutic utility of the information. Somatic mutations in genes of the isocitrate dehydrogenase (IDH) enzyme family appear to be among the best-defined biomarkers that also influence tumor behavior and confer clinical utility. Methods - We have reviewed the literature including our own results to summarize basic science and clinical correlates of IDH mutations. Results - The surveyed data reveal genomic, transcriptomic, epigenomic and biochemical consequences of IDH mutations in the context of glioblastoma biology and phenotype. In addition, a few studies highlight the therapeutic potential of targeting IDH, although thus far all tests have only been conducted in the preclinical setting. Conclusions - Somatic mutations in isoforms of IDH genes represent important biomarkers that correlate with biochemical, biological and phenotypic features of glioblastoma, and may also facilitate the development of new therapeutic strategies complementing the currently available approved protocols.

Clinical Neuroscience

[Early experience with minimal invasive treatment of thirty-one thoracolumbar injury cases]

VARGA Ádám, VERES Róbert, ELEK Péter, MENCSER Zoltán, RIDEG Zoltán, BARZÓ Pál

[A szerzők 31 thoracolumbalis gerincsérült minimálisan invazív műtéti ellátásával szerzett tapasztalataikról számolnak be. A betegek orvosi dokumentációját, radiológiai (preoperatív CT és MRI, valamint posztoperatív CT három és hat hónap után) képanyagát retrospektíven elemzik. A be-avatkozások során minden behelyezett csavar megfelelő pozícióba került, idegrendszeri funkcióromlás és sebfertőzés nem fordult elő. Az utánkövetés során három esetben alakult ki radiológiai korrekcióvesztés, melynek azonban klinikai következménye nem volt. Csavarlazulást, a fémanyag törését nem észleltük. Saját tapasztalataink alapján, a nemzetközi irodalmi adatokkal egybevágóan, a mini-málisan invazív módszer alkalmazását a gerincsérültek ellátása során javasoljuk.]

Clinical Neuroscience

Can high uric acid levels be an independent risk factor for acute ischemic stroke due to large-artery atherosclerosis?

ACAR Türkan, ARAS Guzey Yesim, GÜL Sinem Sidika, ACAR Atılgan Bilgehan

Introduction - Uric acid is a molecule that is known to act as a natural antioxidant in acute oxidative stress conditions such as acute ischemic stroke (AIS). Although there are several studies on the prognostic value of serum uric acid (UA) level, especially the AIS, its importance in ischemic stroke is still controversial. Our aim in this study is to investigate whether the serum UA level is an indicative biomarker in the large-artery atherosclerosis in the AIS etiology. Material and method - Of the patients admitted to Sakarya University Training and Research Hospital Depart-ment of Neurology between January 2017 and November 2017, 91 hospitalized patients, who had AIS diagnosis and had their uric acid levels measured, were analyzed retrospectively. Patients with diabetes mellitus (DM), hypertension (HT), smoking habit, obesity, gout, hyperlipidemia (HL) and renal failure were excluded from the study. Patients were classified as anterior system and posterior system infarct. Then, patients were divided into two groups, one with internal carotid artery (ICA) > 50% stenosis and the other with ICA < 50% stenosis according to carotid-vertebral artery doppler USG examination performed for etiology. Serum UA, total bilirubin, direct bilirubin and indirect bilirubin levels of both groups were statistically compared. Results - In the comparison of serum UA values of ICA>50% stenosis and ICA<50% stenosis group of AIS patients, a statistically significant difference was found between the UA levels (p<0.000), but there was no difference between total bilirubin, direct bilirubin and indirect bilirubin values (p>0.05). Conclusion - High uric acid levels can be considered an independent, indicative risk factor for large-artery disease in AIS.

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Management of bone metabolism in epilepsy

UÇAN TOKUÇ Ezgi Firdevs , FATMA Genç, ABIDIN Erdal, YASEMIN Biçer Gömceli

Many systemic problems arise due to the side effects of antiepileptic drugs (AEDs) used in epilepsy patients. Among these adverse effects are low bone mineral density and increased fracture risk due to long-term AED use. Although various studies have supported this association with increased risk in recent years, the length of this process has not been precisely defined and there is no clear consensus on bone density scanning, intervals of screening, and the subject of calcium and vitamin D supplementation. In this study, in accordance with the most current recommendations, our applications and data, including the detection of possible bone mineralization disorders, treatment methods, and recommendations to prevent bone mineralization disorders, were evaluated in epilepsy patients who were followed up at our outpatient clinic. It was aimed to draw attention to the significance of management of bone metabolism carried out with appropriate protocols. Epilepsy patients were followed up at the Antalya Training and Research Hospital Department of Neurology, Epilepsy Outpatient Clinic who were at high risk for osteoporosis (use of valproic acid [VPA] and enzyme-inducing drugs, using any AED for over 5 years, and postmenopausal women) and were evaluated using a screening protocol. According to this protocol, a total of 190 patients suspected of osteoporosis risk were retrospectively evaluated. Four patients were excluded from the study due to secondary osteoporosis. Of the 186 patients who were included in the study, 97 (52.2%) were women and 89 (47.8%) were men. Prevalence of low bone mineral density (BMD) was 42%, in which osteoporosis was detected in 11.8% and osteopenia in 30.6% of the patients. Osteoporosis rate was higher at the young age group (18-45) and this difference was statistically significant (p=0.018). There was no significant difference between male and female sexes according to osteoporosis and osteopenia rates. Patients receiving polytherapy had higher osteoporosis rate and lower BMD compared to patients receiving monotherapy. Comparison of separate drug groups according to osteoporosis rate revealed that osteoporosis rate was highest in patient groups using VPA+ carbamazepine (CBZ) (29.4%) and VPA polytherapy (19.4%). Total of osteopenia and osteoporosis, or low BMD, was highest in VPA polytherapy (VPA+ non-enzyme-inducing AED [NEID]) and CBZ polytherapy (CBZ+NEID) groups, with rates of 58.3% and 55.1%, respectively. In addition, there was no significant difference between drug groups according to bone metabolism markers, vitamin D levels, and osteopenia-osteoporosis rates. Assuming bone health will be affected at an early age in epilepsy patients, providing lifestyle and diet recommendations, avoiding polytherapy including VPA and CBZ when possible, and evaluating bone metabolism at regular intervals are actions that should be applied in routine practice.

Clinical Neuroscience

[Personalised epilepsy treatment]

ALTMANN Anna

[Epilepsy is one of the most common chronic neurological disease in childhood. Patients with epilepsy – even with so-called benign epilepsy – need medication for years. During this time, children go through a very big change, not only gaining weight and height, but also changing hormonal and metabolic processes. Maturation processes in different brain areas also take place at different rates depending on age. All of these should be considered when preparing a therapeutic plan. In everyday practice after the diagnosis of epilepsy, the applied drug is most often selected based on the shape and type of seizure. However, a number of other factors need to be considered when designing a therapeutic strategy: 1. efficacy (form of epilepsy, type of seizure), 2. age, gender, 3. pharmacological properties of the drug, 4. adverse drug reaction profile, 5. lifestyle (community), figure (skinny, corpulent, obese), 6. other comorbidities (nutrition, behavioral and learning problems, circulatory disorders, kidney or liver disease), 7. expected interactions with other drugs already used, 8. genetics, 9. other aspects (drug registration and prescription rules). The purpose of this article is to help to decide which antiepileptic drugs are expected to have the least side effects in a particular child with different comorbidities and which medications should be avoided if possible.]

Lege Artis Medicinae

[RECENT TRENDS IN THE PHARMACOLOGICAL TREATMENT OF EPILEPSY]

SZUPERA Zoltán

[Over the last decades, drug therapy for epilepsy has changed substantially, which generated new expectations. The first-line therapy of epilepsies is pharmacological treatment, which is effective in 60 to 70% of patients. Despite this favourable result, even today's drug therapy cannot yet be considered optimal. Prior to 1990, only six major antiepileptics were available for the clinicians, while since then more than ten new drugs have been introduced into the market. The older drugs have the advantage of long-term experience, known efficacy, and lower cost. These first generation drugs, while effective in patients with newly diagnosed epilepsy, share some unfavourable properties. They do not control many patients adequately, while with their long-term use chronic side effects develop. The purpose of this paper is to summarize recent data on the efficacy, safety, and administration of the older and new antiepileptic drugs. The main factors to consider when choosing a drug for treatment include syndromatological classification of the disease, efficacy and tolerability of the drug, and individual patient considerations. Of the first generation antiepileptics, carbamapezine, valproate, ethosuximide, and to some extent the clobazam and clonazepam are still widely used (benzodiazepines only as adjunctive therapy). The use of phenobarbitals, primidone, phenytoin, and sulthiam has diminished because of their side effects and inadequate efficacy. New antiepileptics are more efficient primarily in the therapy of West syndrome, Lennox-Gastaut syndrome, and in idiopathic generalized epilepsies. The pharmacokinetic properties of gabapentin, lamotrigine, levetiracetam, and oxcarbazepine are favourable, and their clinical use is safe. The use of felbamate, vigabatrin, and topiramate requires close attention because of their side effects.]

Clinical Neuroscience

[Antiepileptic drugs in treatment of epilepsy and follow up of their efficacy]

GYIMESI Csilla, BÓNÉ Beáta, TÓTH Márton, HORVÁTH Réka, KOMOLY Sámuel, JANSZKY József

[Epilepsy is one of the most common neurological diseases usually demanding long term treatment. The prime goal of therapy is to achieve seizure freedom with avoidance of side effects. Precise diagnosis is fundamental selecting the proper antiepileptic drug(s). In addition of wide-spectrum antiepileptics, selective syndrome-specific antiepileptic drugs are available. Pharmacological features of the new antiepileptics allow more personalized clinical use. Aim of this paper is to provide a comprehensive pragmatic review of therapeutic possibilities and recommendations currently accessible in Hungary.]

Clinical Neuroscience

[Questions of epileptogenesis and prevention in symptomatic epilepsies]

NIKL János

[Symptomatic epilepsies usually report themselves after a longer period of time after brain injury, after the so-called latent period. During this period progressive functional and structural changes occur which finally cause an increased excitatory condition. The process of epileptogenesis may be examined in animal models, such as in the kindling, status epilepticus, hypoxicischaemic models. Data gained from such sources support the hypothesis that the first injury results in a lower seizure threshold, but genetical and enviromental factors also contribute to the development of epilepsy and most probably further insults may be needed. The development of epilepsy can be traced back to several reasons. In spite of this, the latent period provides opportunity for the prevention of epilepsy or for the influence of epileptogenesis in such a manner that later treatment can become more succesful. Prevention should be an aim in clinical practice, as well. Medication used presently are more like to have anticonvulsive properties and their antiepileptogenic effect is questionable. Due to this fact, development of new drugs is necessary with new theoretical background. The most important influence on the incidence of epilepsy in recent years has been provided by the improvement in neonatal care. This highlights the fact that such optimal medical care should be provided in the acute period of brain injury which can terminate or lessen the risk of epilepsy.]