Clinical Neuroscience

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

JANSZKY József, HORVÁTH Réka, KOMOLY Sámuel

MAY 30, 2015

Clinical Neuroscience - 2015;68(05-06)

DOI: https://doi.org/10.18071/isz.68.0149

[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

[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.]

Clinical Neuroscience

Altered BOLD response within the core face-processing network in congenital prosopagnosia

NÉMETH Kornél, ZIMMER Márta, NAGY Krisztina, BANKÓ Éva, VIDNYÁNSZKY Zoltán, VAKLI Pál, KOVÁCS Gyula

Background and purpose - Congenital prosopagnosia is a life-long disorder of face perception. To study the neural backgrounds of congenital prosopagnosia we measured the blood oxygen level-dependent response of congenital prosopagnosic participants, using functional magnetic resonance imaging. Methods - We tested three persons of the family (father, daughter and son), having symptoms of congenital prosopagnosia, as well as healthy controls, using combined neuropsychological and functional magnetic resonance imaging methods. To reveal the neural correlates of the impairments, blood oxygen level-dependent responses within the occipito-temporal cortex were measured to faces and nonsense object images in a block-design experiment. Results - Neuropsychological tests demonstrated significant impairments of face perception/recognition in each subject. We found that the activity of the fusiform and occipital face areas as well as of the lateral occipital cortex was significantly reduced in congenital prosopagnosic participants when compared to controls. Analysis of the hemodynamic response function revealed a lower peak response, but also a significantly faster and stronger decay of the blood oxygen level-dependent response in the occipito-temporal areas in congenital prosopagnosic participants when compared to controls. Conclusion - Our results emphasize the dysfunction of the core face processing system, as well as the lateral occipital complex, in congenital prosopagnosia. Further, the functional impairment of these areas is signalled best by the altered hemodynamic response function, showing abnormally low initial peak and stronger and faster decay in the later parts of the blood oxygen level-dependent response.

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

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

[Acoustic CR®-neuromodulation - first experiencies in Hungary with novel patented method in therapy of chronic subjectiv tinnitus]

BENCSIK Beáta, GÁBORJÁN Anita, HARNOS Andrea, LÁSZLÓ Klára, VÉGSŐ Péter, TAMÁS László

[Objective - Acoustic CR®-neuromodulation is a novel patented method for the therapy of chronic subjective tinnitus and has been tested in Hungary, as one of the first European countries introducing this procedure. It can be used for the treatment of monaural or binaural tonal tinnitus. Suitability of patients for this therapy was assessed by the help of an appropriate set of criteria. Aim of our study was to analyze 6-month therapy and related measurement data of patients first treated with this method in Hungary and evaluate the results. Method - 27 outpatients (20 males, seven females) with a minimum of 6-month long history of subjective tinnitus were assessed (four detected on the right side, six on the left side, 17 on both sides) who were treated for six months by Acoustic CR®-neuromodulation. On 44 treated ears (21 right, 23 left), changes of tinnitus frequency and loudness were measured and analysed, using Visual Analogue Scale (VAS) loudness/annoyance/pitch scores and Tinnitus Handicap Inventory tests, which were performed at defined intervals during the treatment period. Results - During this 6-month treatment period, significant decrease was detected in tinnitus frequency and loudness by tinnitometry (irrespective of the affected side), and an improvement in VAS annoyance/pitch scores and THI test results. VAS loudness did not show any significant changes. Conclusion - Acoustic CR®-neuromodulation therapy may be a useful treatment of subjective chronic tinnitus, but its efficacy should be proved in controlled clinical trials.]

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Clinical Neuroscience

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

YASAR Altun, ERDOGAN Yasar

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]

RAJNA Péter

[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.

Clinical Neuroscience

EEG-based connectivity in patients with partial seizures with and without generalization

DÖMÖTÖR Johanna, CLEMENS Béla, EMRI Miklós, PUSKÁS Szilvia, FEKETE István

Objective - to investigate the neurophysiological basis of secondary generalization of partial epileptic seizures. Patients and methods - inter-ictal, resting-state EEG functional connectivity (EEGfC) was evaluated and compared: patients with exclusively simple partial seizures (sp group) were compared to patients with simple partial and secondary generalized seizures (spsg group); patients with exclusively complex partial seizures (cp group) were compared to patients with cp and secondary generalized seizures (cpsg group); the collapsed sp+cp group (spcp) was compared to those who had exclusively secondary generalized seizures (sg group). EEGfC was computed from 21-channel waking EEG. 3 minutes of waking EEG background activity was analyzed by the LORETA Source Correlation (LSC) software. Current source density time series were computed for 23 pre-defined cortical regions (ROI) in each hemisphere, for the 1-25 Hz very narrow bands (1 Hz bandwidth). Thereafter Pearson correlation coefficients were calculated between all pairs of ROI time series in the same hemisphere. Z-scored correlation coefficients were compared at the group level (t-tests and correction for multiple comparisons by local false discovery rate, FDR). Results - Statistically significant (corrected p<0.05) EEGfC differences emerged at specific frequencies (spsg > sg; cpsg > cp), and at many frequencies (sg > spcp). The findings indicated increased coupling between motor cortices and several non-motor areas in patients with partial and sg seizures as compared to patients with partial seizures and no sg seizures. Further findings suggested increased coupling between medial parietal-occipital areas (structural core of the cortex) and lateral hemispheric areas. Conclusion - increased inter-ictal EEGfC is associated with habitual occurrence of secondary generalized seizures.