Clinical Neuroscience

[Proconvulsive effect of antiepileptic drugs]


MARCH 25, 2015

Clinical Neuroscience - 2015;68(03-04)

[Antiepileptic drugs can provoke and worsen seizures, what is called paradoxical effect. Paradoxical seizure worsening can occur as a nonspecific manifestation of drug intoxication in number of antiepileptic drugs. The other type is a specific type, when antiepileptic drugs with pure GABAergic and sodium channel blocker mechanism of action provoke myoclonic, absence and atonic seizures in specific epilepsy syndromes, mainly in idiopathic generalized epilepsies. Antiepileptic drug-induced exacerbation of seizures is a common, often unrecognized clinical problem, which can be avoided by a careful syndromic diagnosis and by using broad spectrum antiepileptic drugs.]



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TAJTI János, RAJNA Péter

Clinical Neuroscience

[Teriflunomide: new oral immunmodulant drug in therapy of multiple sclerosis]

BENCSIK Krisztina, RÓZSA Csilla, VÉCSEI László

[Multiple sclerosis (MS) is the autoimmune, demyelinating, neurodegenerative disorder of the central nervous system (CNS). There are nine drugs available in Hungary reimbursed by the National Health Insurance Fund of Hungary (OEP) to reduce the activity of the disease, from which seven can be used as first line therapies. We have approximately 20 years of experience with the interferon b-1a/1b and glatiramer-acetate products. Though in case of approximately 30% of the patients using one of the first line drugs, the disease remains active, that we call break-through disease. The reasons for break-through disease could be the insufficient adherence and compliance, the appearance of neutralizing antibodies or the high activity of the disease. One of the oral immunomodulating drugs for MS, teriflunomide, was registered in Europe in 2013. Because of the anti-proliferative and anti-inflammatory effect of teriflunomide, it can be used for the reduction of the disease activity in the relapsing-remitting course of MS. The effect of teriflunomide was proved in one Phase II. and four Phase III. (TEMSO, TOWER, TENERE, TOPIC) studies. Teriflunomide 14 mg once daily was able to demonstrate in two consecutive placebo-controlled phase 3 clinical trials that significantly reduces the relapse rate (31.5% and 36.3%) and in both studies significantly reduces the sustained disability progression (29.8% and 31.5%) moreover delays the appearance of the clinically definitive MS in patients with clinically isolated syndrome (CIS). According to the TENERE study there were no significant differences observed between teriflunomide 14 mg and IFNb-1a s.c. in time to failure and annualized relapse rate but the treatment satisfaction domains of global satisfaction, side-effects and convenience were significantly improved with teriflunomide compared with s.c. IFNb-1a. ]

Clinical Neuroscience

[Drug therapy of neuropathic pain in mirror of latest reccommandations]

KISS Gábor

[Neuropathic pain is considered as a special type of different pain conditions. It’s pathophysiological basis and treatment is completely different from the nociceptive pain. The first comprehensive therapeutic guidelines published approximately a decade ago recommended tricyclic antidepressants, anticonvulsants and opioids. The recent summary presents and evaluates national and international guidelines issued in the last five years. The most frequently suggested drugs by all guidelines are amitriptyline, duloxetine, gabapentin and pregabalin. Pregabalin is the only drug that is recommended first line in all guidelines referred. Opioids are in the second or third line. There seems to be no major development in the pharmacological treatment of the neuropathic pain compared to the earlier recommendations. High quality studies of head to head comparisons and effectiveness of combination therapy are still lacking.]

Clinical Neuroscience

[Do previous offences predict violent acts in psychiatric patients? A retrospective study in Hungary]

BARAN Brigitta, SZABÓ Ádám Ferenc, KARA Borbála, KOVÁCS Magdolna, UZONYI Adél, ANTAL Albert, UNGVARI S Gabor, GAZDAG Gábor

[Aim - To investigate the presence of offences in the previous past history of perpetrators of violent acts who have undergone forced medical treatment. Methods - The documentation of all patients released over a 10-year period from the National Institute of Forensic Psychiatry (IMEI) was reviewed. A comparison was drawn between patients who were convicted of any type of offense before the violent act (patients with previous offences-PPO) and those who were not (patients with no previous offences-PNO). Results - Eighty-six (29%) and 208 (71%) patients formed the PPO and PNO groups, respectively. Prior contact with psychiatric services was significantly higher in the PPO group (p=0.038) and this group was also more likely to offend under the influence of a psychoactive substance (p<0.001). Exceptional brutality and other qualifying factors were more frequent in the PNO group (p=0.019). Conclusion - As IMEI is the only forensic institution in Hungary, the picture presented here reflects the situation in the entire country. A recidivism rate of 29% is within the internationally published range. ]

Clinical Neuroscience

[Effects of maternal epilepsy and antiepileptic therapy in women during pregnancy]

VANYA Melinda, ÁRVA-NAGY Nóra, SZILI Károly, SZOK Délia, BÁRTFAI György

[Objective - The aim of this study was to analyse the effects of epilepsy and antiepileptic drug (AED) treatment on pregnancy and the perinatal outcome, retrospectively. Methods - We examined the obstetric and fetal outcomes among women with epilepsy (WWE), who were followed-up at the Department of Neurology, and who delivered at the Department of Obstetrics and Gynaecology (n=91) between 31th December 2000 and 31th March 2014. Statistical comparisons of different obstetric and fetal parameters on a sample of 91 WWE and 182 non-WWE were assessed by the chi-square-test, the independent sample t-test. Results - The rate of major congenital malformations (MCMS) among the newborns of all AEDs exposed mothers was 7.69%. There were three peaks of seizures: during the third trimester, during delivery and in the puerperium. The prevalence of miscarriages, post-term birth and the rate of caesarean section were significantly higher among the WWE than among the non-WWE (p=0.001; p<0.001; p=0.02). Parameters of neonates (birth weight, birth length, head-, and chest circumference) were significantly different between the WWE group and the non-WWE group (p=0.003, p<0.001, p<0.001, p<0.001) Conclusions - In contrast with recent publications, there were significant differences in the parameters of neonates between the two groups. Our results are in accordance with those of previous studies from the aspect of AED-related MCM, the elevated risk of miscarriages and pre-existing hypertension. ]

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Clinical Neuroscience

Effects of valproate, carbamazepine and levetiracetam on Tp-e interval, Tp-e/QT and Tp-e/QTc ratio


Aim - To evaluate P-wave dispersion before and after antiepileptic drug (AED) treatment as well as to investigate the risk of ventricular repolarization using the Tpeak-Tend (Tp-e) interval and Tp-e/QT ratio in patients with epileptic disorder. Methods - A total of 63 patients receiving AED therapy and 35 healthy adults were included. ECG recordings were obtained before and 3 months after anti-epileptic treatment among patients with epilepsy. For both groups, Tp-e and Tp-e/QT ratio were measured using a 12-lead ECG device. Results - Tp-e interval, Tpe/QT and Tp-e/QTc ratios were found to be higher in the patient group than in the control group (p<0.05, for all), while QTmax ratio was significantly lower in the patient group. After 3 months of AED therapy, significant increases in QT max, QTc max, QTcd, Tp-e, Tp-e/QT, and Tp-e/QTc were found among the patients (p<0.05). When the arrhythmic effects of the drugs before and after treatment were compared, especially in the valproic acid group, there were significant increases in Tp-e interval, Tp-e/QT and Tp-e/QTc values after three months of treatment (p<0.05). Carbamazepine and levetiracetam groups were not statistically significant in terms of pre- and post-treatment values. Conclusions - It was concluded that an arrhythmogenic environment may be associated with the disease, and patients who received AED monotherapy may need to be followed up more closely for arrhythmia.

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

[Decisional collisions between evidence and experience based medicine in care of people with epilepsy]


[Background – Based on the literature and his long-term clinical practice the author stresses the main collisions of evidence and experience based medicine in the care of people with epilepsy. Purpose – To see, what are the professional decisions of high responsibility in the epilepsy-care, in whose the relevant clinical research is still lacking or does not give a satisfactory basis. Methods – Following the structure of the Hungarian Guideline the author points the critical situations and decisions. He explains also the causes of the dilemmas: the lack or uncertainty of evidences or the difficulty of scientific investigation of the situation. Results – There are some priorities of experience based medicine in the following areas: definition of epilepsy, classification of seizures, etiology – including genetic background –, role of precipitating and provoking factors. These are able to influence the complex diagnosis. In the pharmacotherapy the choice of the first drug and the optimal algorithm as well as the tasks during the care are also depends on personal experiences sometimes contradictory to the official recommendations. Same can occur in the choice of the non-pharmacological treatments and rehabilitation. Discussion and conclusion – Personal professional experiences (and interests of patients) must be obligatory accessories of evidence based attitude, but for achieving the optimal results, in some situations they replace the official recommendations. Therefore it is very important that the problematic patients do meet experts having necessary experiences and also professional responsibility to help in these decisions. ]

Clinical Neuroscience

[LADA type diabetes, celiac diasease, cerebellar ataxia and stiff person syndrome. A rare association of autoimmune disorders]

SOÓS Zsuzsanna, SALAMON Mónika, ERDEI Katalin, KASZÁS Nóra, FOLYOVICH András, SZŰCS Anna, BARCS Gábor, ARÁNYI Zsuzsanna, SKALICZKI József, VADASDI Károly, WINKLER Gábor

[Celiac disease - in its typical form - is a chronic immunemediated enteropathy with typical clinical symptoms that develops against gliadin content of cereal grains, and is often associated with other autoimmune diseases. In cases of atypical manifestation classic symptoms may be absent or mild, and extra-intestinal symptoms or associated syndromes dominate clinical picture. The authors present a longitudinal follow-up of such a case. A 63-years old woman was diagnosed with epilepsy at the age of 19, and with progressive limb ataxia at the age of 36, which was initially thought to be caused by cerebellar atrophy, later probably by stiff person syndrome. At the age 59, her diabetes mellitus manifested with type 2 diabetic phenotype, but based on GAD positivity later was reclassified as type 1 diabetes. Only the last check-up discovered the celiac disease, retrospectively explaining the entire disease course and neurological symptoms. By presenting this case, the authors would like to draw attention to the fact that one should think of the possibility of celiac disease when cerebellar ataxia, progressive neurological symptoms and diabetes are present at the same time. An early diagnosis may help to delay the progression of disease and help better treatment.]

Clinical Neuroscience

Relationship between Status Epilepticus Severity Score and etiology in adult NCSE patients

GENC Fatma, ERDAL Abidin, AKCA Gizem, KARACAY Ertan, GÖKSU Özaydın Eylem, KUTLU Gülnihal, GÖMCELI Bicer Yasemin

Purpose - Nonconvulsive status epilepticus (NCSE) is a heterogeneous, severe neurological disorder of different etiologies. In this study, the outcomes of NCSE episodes was assessed in a large series of adult patients. Our objective was to evaluate relationship between Status Epilepticus Severity Score (STESS) and etiology and the role of etiological factors on predicting the outcomes. Method - In this retrospective study, the medical records of 95 patients over 18 years of age who were diagnosed with NCSE between June 2011 and December 2015 were reviewed. Their treatment and follow-up for NCSE was performed at the Epilepsy Unit in Department of Neurology, Antalya Research and Training Hospital. Etiological factors thought to be responsible for NCSE episodes as well as the prognostic data were retrieved. The etiological factors were classified into three groups as those with a known history of epilepsy (Group 1), primary neurological disorder (Group 2), or systemic/unknown etiology (Group 3). STESS was retrospectively applied to patients. Results - There were 95 participants, 59 of whom were female. Group 1, Group 2, and Group 3 consisted of 11 (7 female), 54 (33 female), and 30 (19 female) patients, respectively. Of the 18 total deaths, 12 occurred in Group 2, and 6 in Group 3. The negative predictive value for a STESS score of ≤ 2 was 93.88% (+LR 2.05 95% CI: 1.44-2.9 and -LR 0.3 95% CI 0.10-0.84 ) in the overall study group. While the corresponding values for Group 1 (patients with epilepsy), Group 2 (patients with primary neurological disorder), and group 3 (patients with systemic or unknown etiology) were 100%, 92.59% (+LR 2.06 95%CI: 1.32-3.21 and -LR 0.28 95% CI 0.08-1.02 ) 83.33% (+LR 1.14 95%CI: 0.59-2.9 and -LR 0.80 95% CI 0.23-2.73). Conclusions - This study included the one of the largest patients series ever reported in whom STESS, a clinical scoring system proposed for use in patients with status epilepticus, has been implemented. Although STESS appeared to be quite useful for predicting a favorable outcome in NCSE patients with epilepsy and primary neurological disorders, its predictive value in patients with systemic or unknown etiology was lower. Further prospective studies including larger NCSE samples are warranted.