Clinical Neuroscience

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


MAY 30, 2015

Clinical Neuroscience - 2015;68(05-06)


[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.]



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Clinical Neuroscience

Watershed infarction in hypereosinophilic syndrome: a diagnostic dilemma in FIP1L1-PDGFR alpha-associated myeloid neoplasm

IMELDA Marton, PÓSFAI Éva, ANNUS János Kristóf, BORBÉNYI Zita, NEMES Attila, VÉCSEI László, VÖRÖS Erika

Introduction - The FIP1L1-PDGFR alpha-positive, hypereosinophilic syndrome (HES) is a new category of hematological entities. Various clinical symptoms may occur, with no specific characteristics in either the clinical picture or the neuroimaging findings, and this may give rise to a diagnostic dilemma. A report on a long follow-up period (10 years) in a case of HES that presented with neuropsychiatric symptoms appears to be unique. Besides the complexity of the diagnostic process, the successful treatment is discussed. Case report - The HES was diagnosed in a male patient at the age of 33 years, with involvement of the central nervous system and the myocardium. After the onset of the clinical signs, the MRI indicated bilateral cerebral and cerebellar cortico-subcortical lesions involving the watershed areas, mainly in the parieto-occipital regions. High-dose intravenous steroid (methylprednisolone 500 mg/day) alleviated the neurological symptoms within a few weeks, and the administration of imatinib (200 mg/day) resulted in an impressive regression of the hypereosinophilia and splenomegaly within 6 weeks. During the follow-up, the patient has continued to receive imatinib. The molecular remission has persisted, no new complaints have developed and the condition of the patient has remained stable. Conclusion - The timely recognition of the HES and identification of the disease subtype which led to the administration of imatinib may be the key to successful treatment. The long stable follow-up period gives rise to a new dilemma in the treatment of the HES in these special cases: for how long should a patient receive a tyrosine kinase inhibitor, and may the treatment be suspended?

Clinical Neuroscience

[Alemtuzumab: benefits and challenges of new therapy in multiple sclerosis]

ILLÉS Zsolt, TOBIAS Sejbaek, CSÉPÁNY Tünde

[The widening spectrum of MS treatment is partially due to increasing knowledge about the pathogenesis of MS. The humanized monoclonal antibody against CD52, alemtuzumab has been approved in Europe for the treatment of MS, which results in long-term depletion of B and T cells due to complement- and antibody-mediated cytotoxicity. Based on phase 2 and 3 clinical trials, alemtuzumab decreases the risk of sustained neurological deficit and progression compared to high-dose subcutaneous interferon- β1a in patients with active relapsing-remitting MS, either treatment-naïve or with breakthrough disease. We review advantages and benefits of the treatment, discuss safety concerns, and present a case to describe practical issues.]

Clinical Neuroscience

[Characteristics and differential diagnostics of sleep related pathological movements. Update 2013]

FALUDI Béla, KOVÁCS Norbert, JANSZKY József, KOMOLY Sámuel

[Wide variety of the movements (from the physiologic body position changes to different pathologic events) can be seen during the sleep period. The most important types of these movements are the sleep related events (from the parasomnias to the restless leg related movements), the movement disorders and the epilepsy related events. To differentiate between these events is required special skill, which is based on appropriate characterisation of the events (for example timing, repetition, pattern), the polysomnographic and video-EEG examination and validated questionnaires (FLEP scale). The appropriate differential diagnostics and therapy must be based on the knowledge of the relationship of the sleep architecture and movement events. This review would like to provide guideline for the understanding and recognizing the nature of the sleep related movements.]

Clinical Neuroscience

Chronic cerebrospinal venous insufficiency - disease or misdiagnosis?

PÁNCZÉL Gyula, SZIKORA István, BERENTEI Zsolt, GUBUCZ István, MAROSFŐI Miklós, KOVÁCS Krisztina, RÓZSA Anikó, RÓZSA Csilla

Background and purpose - Former studies reported internal jugular vein stenosis in patients with multiple sclerosis. We aimed to evaluate if these venous stenoses were real and cerebral venous outflow of patients with multiple sclerosis differed from that of normal controls. Methods - 20 controls were prospectively investigated by angiography and duplex ultrasound. Seven patients with multiple sclerosis underwent angiography in other centers; we reviewed these registrations and performed venous ultrasound examinations. Results - Angiography displayed >50% stenosis of internal jugular vein in 19 controls (69±17% on the right and 73±13% on the left side) and <50% stenosis in 1 control (43.5% and 44.6%). All 7 patients had at least one-sided stenosis. The mean degree of stenosis was 63±16% on the right and 67±13% on the left side. There was no significant difference in the degree of stenosis between patients and controls. However, these “stenoses” disappeared if the contrast agent was injected at a catheter position below the orifice of the subclavian vein during venography. The venous flow volume was also similar between groups: 479.7±214.1 and 509.8±212.0 ml/min (right and left side) in the patients and 461.3±224.3 and 513.6±352.2 ml/min in the control group; p=0.85 and 0.98 (right and left). Color and power duplex imaging also revealed normal blood flow of the internal jugular vein in all patients and controls. Conclusion - The cerebral venous status of patients with multiple sclerosis and controls were similar. The angiographic “stenoses” were virtual, caused by the contrast dilution effect of the non-contrast blood stream of the subclavian vein.

Clinical Neuroscience

[Validation of the Hungarian Unified Dyskinesia Rating Scale]

HORVÁTH Krisztina, ASCHERMANN Zsuzsanna, ÁCS Péter, BOSNYÁK Edit, DELI Gabriella, PÁL Endre, KÉSMÁRKI Ildikó, HORVÁTH Réka, TAKÁCS Katalin, BALÁZS Éva, KOMOLY Sámuel, BOKOR Magdolna, RIGÓ Eszter, LAJTOS Júl

[Background - The Unified Dyskinesia Rating Scale (UDysRS) was published in 2008. It was designed to be simultaneous valid, reliable and sensitive to therapeutic changes. The Movement Disorder Society organizing team developed guidelines for the development of official non- English translations consisting of four steps: translation/back-translation, cognitive pretesting, large field testing, and clinimetric analysis. The aim of this paper was to introduce the new UDysRS and its validation process into Hungarian. Methods - After the translation of UDysRS into Hungarian and back-translated into English, it was reviewed by the UDysRS translation administration team. Subsequent cognitive pretesting was conducted with ten patients. For the large field testing phase, the Hungarian official working draft version of UDysRS was tested with 256 patients with Parkinson’s disease having dyskinesia. Confirmatory factor analyses (CFA) determined whether the factor structure for the valid Spanish UDysRS could be confirmed in data collected using the Hungarian Official Draft Version. To become an official translation, the Comparative Fit Index (CFI) had to be ≥0.90 compared to the Spanish-language version. Results - For the Hungarian UDysRS the CFI was 0.98. Conclusion - The overall factor structure of the Hungarian version was consistent with that of the Spanish version based on the high CFIs for the UDysRS in the CFA; therefore, this version was designated as the Official Hungarian Version Of The UDysRS.]

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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

[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

[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

[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. ]

Clinical Neuroscience

[Radiosurgery of intracerebral cavernomas - Current Hungarian practice]

FEDORCSÁK Imre, NAGY Gábor, DOBAI József Gábor, MEZEY Géza, BOGNÁR László

[Background and purpose - Radiosurgery is an increasingly popular treatment option especially for deep eloquent intracerebral cavernomas that are often too risky for surgical removal, but their re-bleed carries significant risk for persisting neurological deficit. Gamma-radiation based radiosurgery has been being available since 2007 in Hungary in Debrecen. Our aim is to summarize our experience accumulated during the first five years of treatment and to compare it to the international experience. Patient selection and methods - We retrospectively analyzed 51 cavernomas in 45 patients treated between 2008 and 2012 in terms of localization, natural history, and the effect of radiosurgery on re-bleed risk and epilepsy, and its side effects. Results - We treated 26.5% deep eloquent (brainstem, thalamic/basal ganglia) and 72.5% superficial hemispheric cavernomas. The median presentation age was 25 years (13-60) for deep, and 45 years (6-67) for superficial cavernomas. They were treated median of 1 year after presentation. 64.5% of deep cavernomas bled before treatment, the annual risk of first hemorrhage was 2%/lesion, re-bleed risk 21.7%, with 44% persisting morbidity. 13.5% of superficial cavernomas bled prior to treatment, the risk of first bleed was 0.3%, there was no re-bleed, and 35% caused epilepsy. We used GammaART-6000TM rotating gamma system for treatment, marginal dose was 14 Gy (10-16), and treatment volume 1.38-1.53 cm3. Re-bleed risk of deep eloquent lesions fell to 4% during the first two years after treatment and to 0% thereafter, and no hemorrhage occurred from superficial lesions after treatment. Persisting morbidity in deep lesions came from adverse radiation effect in 7% and from re-bleed in 7%, and there was no persisting side effect in superficial cavernomas. 87.5% of cases of epilepsy resistant to medical therapy improved. Radiological regression was found in 37.5% and progression in 2% after treatment. Conclusions - Radiosurgery of cavernomas is safe and effective. Early preventive treatment for deep cavernomas carrying high surgical risk is justified. Moreover, for superficial lesions that are surgically easily accessible radiosurgery also appears to be an attractive alternative.]