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

MARCH 30, 2013

Clinical Neuroscience - 2013;66(03-04)

[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.]

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Clinical Neuroscience

[Inclusion body myositis - a rarely recognized disorder]

DÉZSI Lívia, DANIELSSON Olof, GÁTI István, VARGA Edina, VÉCSEI László

[Inclusion body myositis is the most common disabling inflammatory myopathy in the elderly. It is more frequent in men and after the age of 50 years. Inflammatory and degenerative features coexist. There is a T-cell mediated autoimmunity driven by in situ clonally expanded cytotoxic CD8-positive T-cells invading non-necrotic muscle fibres expressing MHC-I antigen. The hallmarks of degeneration are the deposition of protein aggregates and the formation of vesicles. The course of the disease is slow and the diagnosis is usually set after several years. The muscle weakness and wasting is assymetric, affecting predominantly distal muscles of the upper extremity and proximal muscles of the legs. The signs and clinical course can be characteristic, but the diagnosis is established by muscle biopsy. There is currently no evidence based effective treatment for sIBM. Prednisone, azathioprine, methotrexate, cyclosporine and IFN-β failed. Oxandrolon did not improve symptoms. Treatment with intravenous immunglobuline (IVIG) induced in some patients a transient improvement of swallowing and of muscle strenght, but the overall study results were negative. A T-cell depleting monoclonal antibody (alemtuzumab), in a small uncontrolled study slowed down disease progression for a six-month period. Repeated muscle biopsies showed the reduction of T-cells in the muscle and the suppression of some degeneration associated molecules. An effective therapeutic mean should act on both aspects of the pathomechanism, on the inflammatory and the degenerative processes as well.]

Clinical Neuroscience

[Effects of spinal cord stimulation on heart rate variability in patients with chronic pain]

KALMÁR Zsuzsanna, KOVÁCS Norbert, BALÁS István, PERLAKI Gábor, PLÓZER Enikõ, ORSI Gergely, ALTBACKER Anna, SCHWARCZ Attila, HEJJEL László, KOMOLY Sámuel, JANSZKY József

[Background - Spinal cord stimulation has become an established clinical option for treatment of refractory chronic pain and angina pectoris, but its precise mechanism of action is unclear. We investigated the effect of spinal cord stimulation (SCS) on heart rate variability (HRV) and evaluating its influence on the sympathetic/parasympathetic balance in chronic pain. Materials and purpose - Seven patients (three men, four women) with SCS due to chronic pain were included. The SCS was programmed in three different ways: (i) to stimulate at an amplitude known to generate paresthesias (ON-state), (ii) at a subliminal level (SUB state), or (iii) switched off (OFFstate). HRV analysis was based on 5-min segments of the consecutive normal RR intervals and was performed with custom software (Kubios HRV Analysis). Results - The mean heart rate was higher in ON state compared to SUB state (p=0.018) and the high-frequency component of the HRV was lower in ON compared to OFF period (p=0.043). Other HRV parameters values did not significantly differ during the three tested periods. Conclusion - Spinal cord stimulation in chronic pain seems to be accompanied by reduced parasympathetic tone, unlike SCS in angina pectoris where previous studies found a reduced cardiac sympathetic tone. Our study might lead to understand the mechanism of action of SCS We investigated a relatively small number of patients, which is the main limitation of our study. Thus, further studies with larger number of patients are required for validation of our results.]

Clinical Neuroscience

[10 years, 600 monitoring sessions - our experience with the video EEG monitoring of children]

SIEGLER Zsuzsa, HEGYI Márta, JAKUS Rita, NEUWIRTH Magda, PARAICZ Éva, SZABÓ Léna, FOGARASI András

[Introduction- The only Hungarian video EEG laboratorywhere children of ages 0-18 can be continuously monitoredfor several days was opened 1 June 2001 at Department ofNeurology of Bethesda Children’s Hospital.Objectives- Summarizing our 10 years of experience withthe video EEG monitoring (VEM) of children and defining theplace of VEM in the treatment of childhood epilepsy inHungary.Patients and methods- We have processed data from 597monitoring sessions on 541 patients between June 1, 2001and 31 May, 2011 based on our database and the detailedsummaries of the procedures. Results- 509 patients were under the age of 18. The average length of the sessions was 3.1 days. We haveobserved habitual episodes or episodes in question in 477(80%) sessions. 241 (40%) sessions were requested with anepilepsy surgery indication, and 74 patients had 84 opera-tions. 356 (60%) were requested with a differential diagnosisindication, and 191 (53%) cases of epilepsy werediagnosed. We most commonly diagnosed symptomaticgeneralized epilepsy (57 cases). In 165 sessions the episodein question was not diagnosed as epilepsy. Among theparoxysmal episodes we have identified events ofpsychogenic origin, movement disorders, sleep disordersand behavioral disorders. Only 3% of the differential diag-nosis procedures brought no additional clinical information.Discussion- The diagnostic efficiency in our VEM laborato-ry is in accordance with the data found in the literature.Besides epilepsy surgery VEM is recommended if suspectedepileptic episodes occur and interictal epileptiform signs arenot present or are not in accordance with the symptoms, ifthere is no explanation for therapy resistance and if paroxys-mal episodes of non-epileptic origin are suspected but theycannot be identified based on the anamnesis. VEM is also helpful in diagnosing subtle seizures. The procedure hasnumerous additional benefits in patient care and in trainingthe parents and hospital staff. ]

Clinical Neuroscience

[Efficacy of deep brain stimulation in our patients with Parkinson’s disease]

GERTRÚD Tamás, TAKÁTS Annamária, RADICS Péter, RÓZSA Ildikó, CSIBRI Éva, RUDAS Gábor, GOLOPENCZA Péter, ENTZ László, FABÓ Dániel, ERÕSS Loránd

[Background and purposes - In advanced Parkinson’s disease, medically refractory motor fluctuation or medically resistant tremor considerably affects quality of life. However, these symptoms can be mostly successfully treated by deep brain stimulation. We analyzed the efficacy of bilateral subthalamic stimulation in our patients with Parkinson’s disease. Methods - We assessed the clinical data of ten patients who have been treated in the Department of Neurology, Semmelweis University and have been operated in the National Institute of Neurosciences between 2008 and 2011. The Hoehn-Yahr scale score, the Unified Parkinson’s Disease Rating Scale score and the Parkinson’s Disease Questionnaire 39, as well as the dose of antiparkinson medication were documented prior to and one year after surgery. Results - Patient condition improved according to the Hoehn-Yahr scale, approximately by two stages. The dose of antiparkinson medication could be reduced by 63.4% (p=0.005) post operation. Unified Parkinson’s Disease Rating Scale scores decreased by 70.9% (p=0.005). 12 hours after medication withdrawal, execution of daily activity improved by 57.1% (p<0.01) and motor functions developed by 79.1% (p<0.01). Duration of dyskinesias decreased by 62.5% (p=0.018), duration of akinesia diminished by 87.5% (p=0.005). Quality of life rose by 41.6% (p<0.01). Neuropsychological tests detected improvement in verbal memory. Conclusion - With deep brain stimulation, the dosage of antiparkinson medication could be significantly reduced, with considerable improvements in motor function and quality of life. Although the number of patients is still low, good results have been established by careful patient selection, precise neurosurgical procedure and by appropriate programming and patient care.]

Clinical Neuroscience

[Application of minimally invasive instrumental spine surgery technique in lumbal diseases of degenerative or traumatic origin]

SCHWARCZ Attila, KASÓ Gábor, BÜKI András, DÓCZI Tamás

[Paradigm change has recently taken place in spine surgery with the application of minimally invasive techniques. Minimally invasive techniques have several advantages over the open traditional techniques: less blood loss, preservation of spine muscle integrity, shorter hospitalization, early mobilization, reduced pain levels, lower risk of infection. The presented cases cover following lumbar pathologies: segmental spinal instability, LV-SI grade II. spondylolisthesis, degenerative spondylolisthesis, spine trauma. Unilateral or bilateral mini-open technique was employed in the degenerative cases, depending on symptoms and signes. If unilateral symptoms - pathology was identified, screws and rod were implanted percutaneously on the side contralateral to the pathology. The segmental fusion between vertebral bodies was always assured by a cage and autologous bone. The presented trauma case involved combined AO type A2 and B fractures. The anterior column was strengthened with vertebral body stents filled with bone cement, the posterior column was fixed with a percutaneously implanted screw rod system. Insertion of stents in the collapsed vertebra significantly increased the vertebral body height and also improved the stability of the spine. Minimally invasive spine surgery techniques appear more advantageous over the traditional open spine surgery that necessitates for large midline approaches.]

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Clinical Neuroscience

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

[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.]

Lege Artis Medicinae

[THE USE OF GENERIC DRUGS IN THE MEDICAL THERAPY OF EPILEPSY]

RAJNA Péter

[The author demonstrates the relationship between the innovative and generic antiepileptic drugs regarding the clinical aspects. Among the requirements for the registration of generics one can find small differences in the prescribed and the practical levels of bioequivalence. An important but not widely known fact is that these differences can lead to clinically important alterations if the effects of different generics or the effects on high risk patients are compared. While the increasing market of generics is due to economical factors (and rarely due to medical decisions), the safety of the drugs becomes extremely important. From this aspect, special patient populations eg. children, elderly people or patients with multiple illnesses under multidrug treatment are necessarily of greater medical importance. The characteristics of the antiepileptic drugs on the elderly patients, their increased sensitivity to particular adverse events and the possible somatic side effects are discussed in details. The type of epilepsy also has its special characteristics and is important in the choice of the most successful medicine. The development of the antiepileptic drugs shows a positive direction for their efficacy. In the discussion the author points out three main ways for using generic drugs: prescription of generic drug in monotherapy or as an additive in newly diagnosed patients, the exchange of the innovative agent to a generic and the exchange of one generic to another. The author also mentions the legal points and criticizies the regulations available in some countries allowing a free exchange of the bioequivalent drugs without the agreement of the physician or the patient. The final part of the paper reviews the results of the comparative studies on the effects of the generic antiepileptic drugs and the experiences of the physicians of their application based on surveys performed with questionnaires. The data of the literature is compared to the Hungarian methods of application and to his own experience. Recommendations for the application of generic antiepileptic drugs are summarized in „twelve points“.]