Clinical Neuroscience

[Valproate in the treatment of epilepsy and status epilepticus]

JANSZKY József, TÉNYI Dalma, BÓNÉ Beáta

JULY 30, 2017

Clinical Neuroscience - 2017;70(07-08)


[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. ]



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Clinical Neuroscience

[Guidelines for the treatment of traumatic brain injury - 2017]

BÜKI András, BARZÓ Pál, DEMETER Béla, KANIZSAI Péter, EZER Erzsébet, TÓTH Péter, HORVÁTH Péter, VARGA Csaba

[Traumatic brain injury (TBI) is recognized to be the main cause of death and disability in the first four decades representing a major socio-economical problem worldwide. Recent communications revealed a particularly worrying image about the quality of care for TBI in Hungary. For any improvement a systematic approach characterized by utilization of scientific evidence based guidelines forming the basis for close monitoring of the actual care are considered a prerequisite. In Hungary the first evidence based guidelines in the field of TBI have been issued by the National Society for Anesthesiology and Intensive Care more than two decades ago followed by joint guidelines of the Hungarian Neurosurgical Society and the Hungarian College of Neurosurgeons. These publications were primarily based on the work of the European Brain Injury Consortium as well as guidelines issued by the Brain Trauma Foundation. Recent renewal of the latter and a need to refresh the outdated national guidelines was met by a call from regulatory authorities to issue the updated version of the Hungarian TBI-guidelines. The present review is aimed to briefly summarize the most fundamental elements of the national head injury guidelines that would hopefully be officially issued in a far more detailed format soon.]

Clinical Neuroscience

Validation of the Hungarian version of the Test Your Memory

KOLOZSVÁRI Róbert László, KOVÁCS György Zoltán, SZŐLLŐSI József Gergő, HARSÁNYI Szilvia, FRECSKA Ede, ÉGERHÁZI Anikó

Concerns regarding the projected prevalence of Alzheimer’s disease (AD) over the next several decades have stimulated a need for the detection of AD in its earliest stages. A self-administered cognitive test (Test Your Memory, TYM) is designed as a short, cognitive screening tool for the detection of AD. Our aim was to validate the Hungarian version of the Test Your Memory (TYM-HUN) test for the detection of AD. The TYM-HUN was applied in case of individuals aged 60 years or more, 50 patients with AD and 50 healthy controls were recruited into the study. We compared the diagnostic utility of the Hungarian version of the TYM in AD with that of the Mini-Mental State Examination (MMSE). The sensitivity and specificity of the TYM-HUN in the detection of Alzheimer’s disease were determined. The patients with AD scored an average of 15.5/30 on the MMSE and 20.3/50 on the TYM-HUN. The average score achieved by the members of the healthy control group was 27.3/30 on the MMSE and 42.7/50 on the TYM. The total TYM-HUN scores significantly correlated with the MMSE scores (Spearman’s rho, r=0.8830; p<0.001). Multivariate logistic regression model demonstrated that a one-point increase in the TYM score reduced the probability of having AD by 36%. The optimal cut-off score on the TYM-HUN was 35/36 along with 94% sensitivity and 94% specificity for the detection of AD. The TYM has a much wider scoring range than the MMSE and is also a suitable screening tool for memory problems, furthermore, it fulfils the requirements of being a short cognitive test for the non-specialists. The TYM-HUN is useful for the detection of Alzheimer’s disease and can be applied as a screening test in Hungarian memory clinics as well as in primary care settings.

Clinical Neuroscience

[Systemic thrombolysis after the administration of idarucizumab in acute ischemic stroke]


[Introduction - Expanding indications have resulted in an increasing number of patients taking novel oral anticoagulants, posing a major treatment dilemma in acute ischemic stroke. Case presentation - We present a successful intravenous thrombolysis in a dabigatran-treated patient with acute ischemic stroke after the administration of idarucizumab. Discussion - According to current guidelines, systemic thrombolysis is contraindicated under treatment with novel oral anticoagulants (taken within 48 hours). In this scenario, idarucizumab offers a solution by reversing the anticoagulant effect of dabigatran. Conclusion - Although there have only been case reports published so far, the dabigatran-antidote idarucizumab seems to give new therapeutic opportunities in the treatment of acute ischemic stroke.]

Clinical Neuroscience

[Calcium ion is a common denominator in the pathophysiological processes of amyotrophic lateral sclerosis]

PATAI Roland, NÓGRÁDI Bernát, MESZLÉNYI Valéria, OBÁL Izabella, ENGELHARDT József István, SIKLÓS László

[Amyotrophic lateral sclerosis (ALS), the most frequent motor neuron disease is characterized by progressive muscle weakness caused by the degeneration of the motor neurons in the spinal cord and motor cortex. However, according to the recent observations, ALS is a rather complex syndrome which frequently involves symptoms of cognitive impairment. Therefore, ALS cases can be interpreted in a clinico-pathological spectrum spanning from the classical ALS involving only the motor system to the fronto-temporal dementia. The progression of the disease, however, manifested in the degeneration of the upper and lower motor neurons, is based on the same complex pathobiology. The main elements of the pathomechanism, such as oxidative stress, excitotoxicity, immune/inflammatory processes and mitochondrial dysfunction are well described already, which operate in orchestrated way and amplify the deleterious effect of each other. It is assumed that calcium ions act as a catalyst in this interaction, hence each of the individual mechanisms has strong, positive and reciprocal calcium dependence thus may combine the individual pathological processes into a unified escalating mechanism of neuronal destruction. This review provides an overview of the role of calcium in connecting and amplifying the major mechanisms which lead to degeneration of the motor neurons in ALS. ]

Clinical Neuroscience

[Is second-line immunomodulatory treatment effective in multiple sclerosis?]


[Purpose - Natalizumab is the first evidence based monoclonal antibody, which was launched for treatment in relapsing remitting multiple sclerosis in Hungary in 2010. Standardized follow-up is required to use it. Our aim was to evaluate the efficacy and to monitor the safety of natalizumab treatment by using an electronic database established for MS registry. Clinical activity was measured by annual relapse rates, functional status of patients measured by EDSS and MFSC. Radiological activity was evaluated by standard MRI protocol. Data, results of MS patients and side effects of natalizumab treatment were recorded in iMed software. Results - 31 patients started the natalizumab treatment after 6.5±5.8 years from the onset of MS. The efficacy of treatment was evaluated after a mean of 67 (min: 14 max: 128) infusions in December 2016. The drop-out rate was low, due to the presence of neutralising antibodies in one case, pregnancy in two cases and development of malignant disease in one case which was not related to the natalizumab treatment. The treatment was well tolerated with excellent compliance without serious side effects. The annual relapse rate reduced from a mean of 1.7 to 0.03 (p<0.000001) in the first 12 months of treatment compared to the pretreatment 12 month activity, and it stayed at low level during the whole follow up. EDSS was stable or improved with an exception of two cases. In 23 subjects (77%) lack of new/enlarging T2 lesions and lack of gadolineum-enhancing lesions on MRI were observed. 18 patients (60%) had no evidence of disease activity (NEDA-3). PASAT test improved in most of the cases. Conclusion - The natalizumab therapy was very effective in all cases including those patients who had active disease under the previous immunomodulatory treatment.]

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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

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

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.

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.]