Clinical Neuroscience

[Our clinical experience with zonisamide in resistant generalized epilepsy syndromes]

KELEMEN Anna, RÁSONYI György, NEUWIRTH Magdolna, BARCS Gábor, SZŰCS Anna, JAKUS Rita, FABÓ Dániel, JUHOS Vera, PÁLFY Beatrix, HALÁSZ Péter

MAY 20, 2011

Clinical Neuroscience - 2011;64(05-06)

[Purpose - Zonisamide is licensed in the European Union for adjunctive therapy for partial epilepsy, but its efficacy in generalized epilepsy was less explored. Methods - This prospective observational study included 47 patients (mean age 29 years, range 3-50) with different resistant generalized epilepsy syndromes: idiopathic generalized syndromes (IGE) 15 patients, (juvenile myoclonic epilepsy four, absence epilepsy four, myoclonic absence two, unclassified IGE five), progressive myoclonic epilepsy type 1 (PME1) four, severe myoclonic epilepsy of infancy (SMEI) three, borderline SMEI three, Lennox-Gastaut syndrome/secondary generalized epileptic encephalopties 23 patients. All patients were followed up for at least six months. The mean dose given was 367 mg/day (range 100-600 mg/day), the patients received at least one and no more than two concomitant AE. Response was defined as more than 50% seizure reduction or seizure freedom. Results - The best effect was achieved in PME one, all the patients were responders. Myoclonic seizures were reduced 80%, none of the patients had generalized tonic clonic (GTC) seizures. In two of the four patients all other antiepileptics were tapered of (including piracetam), so they were GTC seizure and almost myoclonia free on zonisamide only. Responder rates were in GEFS ± SME 62.5%, in resistant IGE 62.5%, and in epileptic encephalopathies 33.3% patients. Tolerance after initial efficacy developed in six patients. Adverse effects were mild: weight loss, somnolence and confusion were repeatedly reported. Three patients reported cognitive improvement. Conclusion - Clinical benefit of a broad spectrum antiepileptic zonisamide extends across seizure types, ages and epilepsy syndromes. The efficacy in PME proved to be excellent.]



Further articles in this publication

Clinical Neuroscience

[Excerpts of achievements of pharmaceutical cerebro-vascular protection, with especial regard to the statins]


[Despite that hypercholesterinemia is not a risk factor of stroke, treatment with statins is able to reduce these events in a clinically relevant degree. Intervention trials suggest that while for primary prevention, statins are effective in conventional dose, after stroke or TIA this is true only if LDL-cholesterol is reduced below 1,8 mmol/L. To reach this goal, usually intensive antilipid treatment is necessary. There are studies showing beneficial impacts of other lipid drugs, beyond statins, i.e. fibrates and fish oil (among the settings of primary, and secondary preventions, respectively). Against cerebro-vascular events, pleitropic effects of some antihypertensive and antidiabetic medications can also be established.]

Clinical Neuroscience

[The role of sleep dynamics and delta homeostasis in cognitive functions]


[The paper is aimed to introduce the neuronal network basis of dynamic sleep processes, including the micro-structure of sleep and the relationship of sleep dynamics with homeostatic regulation and plastic changes during sleep. Newer studies tend to show that beyond the wellknown long-term homeostatic and circadian regulation of NREM sleep, sleep is regulated by a stimulus and arousal dependent flexible defense system, the elements of which participate in sleep delta homeostasis. Within the EEG elements of sleep a more larger amount represents reactible type as it was thought previously.. Both the events of wake state and sensory input during sleep are shaping the sleep EEG in a function- and localisation specific way and the next day cognitive functios are determined by these changes.]

Clinical Neuroscience

[Antinociception by endogenous ligands at peripheral level]

HORVÁTH Gyöngyi, MÉCS László

[It is well known that a multitude of ligands and receptors are involved in the nociceptive system, and some of them increase, while others inhibit the pain sensation both peripherally and centrally. These substances, including neurotransmitters, neuromodulators, hormones, cytokines etc., may modify the activity of nerves involved in the pain pathways. It is also well known that the organism can express very effective antinociception in different circumstances, and during such situations the levels of various endogenous ligands change. Accordingly, a very exciting field of pain research relates to the roles of endogenous ligands. The peripheral action may possibly be extremely important, because low doses of the endogenous ligands may reduce pain without disphoric side-effects, and without the abused potential typical of centrally acting ligands. This review provides a comprehensive overview of the endogenous ligands that can induce antinociception, discusses their effects on different receptors and focuses on their action at peripheral level. We found 17 different endogenous ligands which produced antinociception after their topical administration. The results suggest an important direction for the development of pain strategies that focus on the local administrations of different endogenous ligands.]

Clinical Neuroscience

[Neurology 2009: a survey of the neurological capacities, their utilization and neurologists based on the 2009 reports of the institutions in Hungary]


[A detailed information on the quantitative and qualitative features and the regional distribution of the current neurological services at the national level is necessary for the planning of health care provision for the future. We present the characteristics of the current neurological services analyzing the database of the National Health Insurance Fund for 2009. This database is exceptionally large and detailed compared to similar data sources in Europe. We examine the number of patients and cases treated both in hospitals and at outpatient units, and also present the distribution of major diagnoses based on ICD-10. We discuss the major problems in three groups: the decrease of capacities; the fragmentation of capacities; and the uneven distribution of workload on neurologists. Number of neurological hospital beds, weekly hours of neurological outpatient capacity, and the number of neurologists are presented. In the analysis of the utilization of capacities we give the number of patients, the number of cases and the financing of the professional performance. We characterize the workload of neurologists by the mean daily number of patients seen by a neurologist, by the number of outpatient units served by one neurologist during the year, and by the proportion of the total workload on each neurologist. Neurological capacities significantly decreased in the period of 2004-2009: 12 hospital neurological wards were closed, and with further decreases in bed numbers the original 3733 neurological beds decreased to 2812. In four counties - Bács, Heves, Tolna and Vas - only a single neurological ward survived. The capacity withdrawn from inpatient care was not transferred into outpatient services. In 2009 there were 179 hospitals and 419 independent outpatient centers in Hungary. Of the 179 hospitals 55 had neurological beds and a further 42 hospitals offered only outpatient neurological service. Neurological outpatient service is offered in Hungary altogether by 185 institutions: 97 hospitals and 88 independent outpatient centers. Suboptimal outpatient services (less than 30 hours per week) cover 57% of the outpatient capacities. There is an over fivefold difference among counties in capacities: the number of inhabitants per hospital bed ranges between 2167-13 017, and the number of inhabitants per one neurologist outpatient hour between 495-2663. In 2009 there were 1310 board certified neurologists in Hungary, of these only 834 participated at least once during the year in exclusively neurological service, and there was a large difference in workload among individual neurologists. The gross mean income of a 30-hour-per-week average neurological outpatient practice based on performance reports was 871 thousand HUF (about 4350 USD or 3160 EUR) per month. In recent years the neurological capacities significantly decreased and fragmented, do not correspond regionally to the number of population to be served, and their profitability does not cover the conditions of self sufficient operation. This analysis will help health care providers and decision makers to recognize and address the current problems and design the neurological health care system for the coming years.]

Clinical Neuroscience

[Neuropsychiatry - in Hungary and other countries]


All articles in the issue

Related contents

Clinical Neuroscience

[Zonisamide: one of the first-line antiepileptic drugs in focal epilepsy ]


[Chronic administration of antiepileptic drugs without history of unprovoked epileptic seizures are not recommended for epilepsy prophylaxis. Conversely, if the patient suffered the first unprovoked seizure, then the presence of epileptiform discharges on the EEG, focal neurological signs, and the presence of epileptogenic lesion on the MRI are risk factors for a second seizure (such as for the development of epilepsy). Without these risk factors, the chance of a second seizure is about 25-30%, while the presence of these risk factors (for example signs of previous stroke, neurotrauma, or encephalitis on the MRI) can predict >70% seizure recurrence. Thus the International League Against Epilepsy (ILAE) re-defined the term ’epilepsy’ which can be diagnosed even after the first seizure, if the risk of seizure recurrence is high. According to this definition, we can start antiepileptic drug therapy after a single unprovoked seizure. There are four antiepileptic drugs which has the highest evidence (level „A”) as first-line initial monotherapy for treating newly diagnosed epilepsy. These are: carbamazepine, phenytoin, levetiracetam, and zonisamide (ZNS). The present review focuses on the ZNS. Beacuse ZNS can be administrated once a day, it is an optimal drug for maintaining patient’s compliance and for those patients who have a high risk for developing a non-compliance (for example teenagers and young adults). Due to the low interaction potential, ZNS treatment is safe and effective in treating epilepsy of elderly people. ZNS is an ideal drug in epilepsy accompanied by obesity, because ZNS has a weight loss effect, especially in obese patients.]

Clinical Neuroscience

[The role of zonisamide in the treatment of women with epilepsy]


[The antiepileptic drugs can effect fertility, development of gynecological diseases and occurence of sexual problems. They can cause a number of “cosmetic” problem and also influence the selection of safe contraceptive method. Many antiepileptic drugs can cause congenital malformations or affect the new-born child’s psychomotor and cognitive development, therefore during pregnancy should be treated with extreme caution in women with epilepsy. Most types of epilepsies accompany the patient through their whole life. Women spend almost the third of their lives after menopause and - due to the formation of associated diseases as well - this period is also special. According to the 2013 recommendation of International League Epilepsy (ILAE), zonisamide is one of the first-line antiepileptic drugs in focal epilepsy. In my review I discuss women’s epilepsy in the viewpoint of the application of zonisamid. ]

Clinical Neuroscience

[The role of zonisamide in the management of pediatric partial epilepsy]

ROSDY Beáta, KOLLÁR Katalin, MÓSER Judit, MELLÁR Mónika

[In our review we discuss the group of approved antiepileptic drugs for children in Hungary. We cite the results of the review conducted by the International League Against Epilepsy on antiepileptic drug efficacy and effectiveness as initial monotherapy for newly diagnosed epileptic seizures and syndromes in pediatric age group. 25% of pediatric epilepsy is therapy resistant, so we further need new drugs, which must be investigated according to the rules of the European Medicine Agency. The ethical dilemmas of childhood drug studies lead to the situation that the new antiepileptic drugs, approved as monotherapy in adult epilepsies, are in the majority just in add-on regimen tested in pediatric patients. As clinicians we appreciate open label extension safety studies. An old-new antiepileptic drug in Europe is zonisamide. Though it was approved for first line monotherapy in pediatric and adult patients with partial and generalised epilepsy in 1989 in Japan, the European Medicine Agency licensed its use as adjunctive therapy in children aged 6 years or older with partial seizures (with or without secondary generalisation) just in 2013. The results of the openlabel extension study appeared in 2014. The mean dose received was 7.5 mg/kg/day. During the open label phase 11% of the patients achieved seizure freedom and it was maintained throughout the study. The drug was generally well tolerated. The most frequently reported treatment-related adverse events were decreased weight (6%), decreased appetite (4%), and headache (2%). No new or unexpected side effects emerged. In conclusion oral zonisamide as adjunctive therapy in pediatric patients aged 6-17 years with partial seizures demonstrated an acceptable safety and tolerability profile and efficacy over a period at least 1 year. So it is a good treatment option in this population.]

Clinical Neuroscience

[The clinical utility of genetic testing in epilepsy]


[We summarize those epilepsies, in which genetic testing has clinical significance. Different types of genetic tests are presented. Na-channel epilepsies include different clinical entities, the exact genetic diagnosis is relevant in the prognosis, genetic counseling, as well in the therapeutic decision - as Na-channel blockers may worsen them. Molecular genetic tests are available for most of the malformations of cortical development, important for genetic counseling and prenatal diagnosis. Molecular genetic testing of progressive myoclonic epilepsies, which may be difficult to differentiate clinically is almost complete. For some neonatal/infantile epileptic encephalopathies, for most of the neurometabolic disorders, molecular genetic tests are available, so are cytogenetic tests for chromosomal abnormalities accompanied with epilepsy. The clinical significance of the genetic diagnostic of rare, focal inherited epilepsies is limited, their importance is mostly in epilepsy pathophysiology research. The genetic background of the common idiopathic generalized epilepsies is unrevealed so far.]

Clinical Neuroscience

[Valproate in the treatment of epilepsy and status epilepticus]

JANSZKY József, TÉNYI Dalma, BÓNÉ Beáta

[According to Hungarian guidelines, valproate - with the exception of infants and small children as well as fertile women - is the first drug of choice in generalized and unclassified epilepsies because it is effective in most seizure types and epilepsy syndromes. It is highly effective in juvenile myoclonic epilepsy. Even though it is not the first-line drug in focal epilepsies, if the first-line therapy is ineffective, it is a plausible alternative as second choice therapy, owing to its different mechanism of action. If the type of epilepsy can’t be surely established, valproate is the drug of choice, as it possesses the broadest-spectrum among antiepileptic drugs. After administration of benzodiazepines, intravenously applied valproate can be a first choice therapy in all types of status epilepticus, owing to its broad-spectrum and efficacy. Valproate is the first-choice therapy in patients with glioblastoma - independently of the seizure type -, as it is likely to improve the survival rate with 2-10 months and the effectivity of chemo- and radiotherapy. Valproate is generally not suggested for fertile women, but - as it is the most effective therapy in some epilepsy syndromes -, the patient has the right to choose valproate therapy, thus undertaking the elevated risk of developmental abnormalities, for higher safety regarding seizures. If only valproate therapy owns the ability to obtain seizure freedom, then stopping its administration is not suggested, but a low dosage has to be aimed (500-600 mg/day, but not more than 1000 mg/day): according to some studies, most idiopathic generalized epilepsies can be controlled by low valproate dosage. Stopping valproate therapy in case of an ongoing pregnancy is not suggested. ]