Clinical Neuroscience

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

JUHOS Vera

NOVEMBER 30, 2016

Clinical Neuroscience - 2016;69(11-12)

DOI: https://doi.org/10.18071/isz.69.0381

[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. ]

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Clinical Neuroscience

[Ketamine administration in case of severe, therapy resistant depressed patient, case report]

MORVAI Szabolcs, NAGY Attila István, BÁLINT-SZÖLLŐSI Adrienn, MÓRÉ E Csaba, BERECZ Roland, FRECSKA Ede

[Objective - In our case report we present the treatment of a female patient suffering from therapy resistant depression. This procedure is not in practice in Hungary at present, the aim of our work to reproduce the findigs of international studies in domestic circumstances. Matter - Major depression is a common, chronic and severe mental disorder, with 16.2% lifetime prevalence. Many international randomized, placebo controlled trials found administration of ketamine infusion effective in depressed patients. Methods - Since ketamine is an anesthetic agent, its administration was performed in the post-operative monitoring room of our hospital operating-room, supervised by an anesthesiologist. According to formerly published data, a dose of 0.5 mg/kg of body weight was administered intravenously in 40 minutes by perfusor. The drug was administered in a same manner fifteen days later. Subject - The patient was admitted to our inpatient ward with severe depression. During two months of combined antidepressant therapy her condition has not improved significantly. Approval for off label drug indication was granted with urgency by the National Institute of Quality and Organizational Development in Healthcare and Medicines. Results - During the two treatments the Hamilton Depression Rating Scale 21 items rating scale score was reduced to 8 from the baseline 28, the Hamilton Anxiety Rating Scale score was reduced to 6 from 25, Beck Depression Inventory was reduced to 9 from 20. Upon administration of the drug no severe adverse event was detected, the mild dissociative state related to ketamine was ceased in a short period of time. Discussion - With administration of 0.5 mg/kg ketamine the authors managed to achieve rapid improvement in a therapy resistant depressed patient, without permanent side effects. Our future plan is to repeat the use of the drug within a double-blind, placebo controlled trial in order to prove its efficacy in hospital settings. ]

Clinical Neuroscience

[Recommendation for treatment options in advanced Parkinson's disease]

ASCHERMANN Zsuzsanna, DIBÓ György, KLIVÉNYI Péter, KOVÁCS Norbert, KOVÁCS Tibor, TAKÁTS Annamária, GERTRÚD Tamás, VARANNAI Lajos

[The treatment of advanced Parkinson’s disease is challenging for both physicians and caregivers. The device-aided therapies need expertise and dedicated hospital centers. In this summary we have concluded the available data and recommendation for the treatment options in advanced Parkinson’s disease and adopt them to the daily care in Hungary. ]

Clinical Neuroscience

Patient characteristics and the effects of intravenous immunoglobulin in patients with Guillain-Barre syndrome

GUZEY ARAS Yesim, TANIK Osman, DOGAN GÜNGEN Belma, KOTAN Dilcan

Purpose - The purpose of this study is to determine the diagnosis- and treatment-related characteristics in Guillain-Barré syndrome (GBS) and to evaluate the effects of early intravenous immunoglobulin (IVIg) treatment on disability, mortality and prognosis. Materials and methods - Adult patients who were diagnosed with GBS in our clinic between January 2000 and January 2014 were retrospectively scanned. While the patients undergoing IVIg treatment were included in the study, the other neuropathic diseases were excluded. Patients were divided into two groups based on the administration time of the IVIg treatment; Group 1 (<7 days) and Group 2 (≥ 7 days) Group 1 consisted of patients undergoing IVIg treatment within 7 days after presentation of symptoms and Group 2 consisted of patients undergoing IVIg treatment on and after 7th day following presentation of symptoms. The scores from Hughes Functional Grading Scale (HFGS) on admission and one month laterwere recorded in all patients in order to evaluate the disability and prognosis in terms of demographic and clinical laboratory characteristics. Results - In this study, 49 GBS patients were included (31 patients in Group 1 and 18 patients in Group 2). Demyelinating form of GBS was determined in 22 (44.8%) patients.). While there was no difference between both groups (p: 0.288, p: 0.762, p: 0.693 respectively) in terms of intensive care and rehabilitation requirement and progression, only 2 patients in Group 1 died. While HFGS mean score on admission in all the patient groups was 3.27±0.974, their HFGS mean score at month 1 was 2.53±1.226. There was no difference between the groups in terms of HFGS mean scores on admission and at month 1. Within each groups, there was a significant improvement between initial (on admission) HFGS scores and HFGS scores acquired at month 1. Conclusion - In this study, demyelinating form was more frequent than axonal form. A total of 2 g/kg dose of IVIg treatment administered for 5 days as a standard in GBS patients ensured a significant improvement on both disability and early and late administration and early administration of the treatment does not lead to any difference in intensive care unit and rehabilitation requirements.

Clinical Neuroscience

Vitreous humor diffusion measurements from diffusionweighted imaging in idiopathic intracranial hypertension

CAGLI Bekir, TUNCEL Alpaslan Sedat, YILMAZ Erdem, TEKATAS Aslan, ERMIS Veli

Background - Idiopathic intracranial hypertension is a disease with uncertain etiology. It is not caused by an intracranial mass lesion or hydrocephalus and is characterized by abnormal elevation of intracranial pressure and normal composition of the cerebrospinal fluid. The orbita and intracranial area are closely related anatomically. Elevated intracranial pressure can be transmitted to the orbita through the cerebrospinal fluid around the optic nerve sheath changes at the vitreous humor on diffusion-weighted imaging have not been systemically studied in idiopathic intracranial hypertension. Purpose - The purpose of this study was to investigate diffusion changes in the vitreous humor in patients with intracranial hypertension. Methods - In this retrospective study, 25 patients with papilledema and who had been definitively diagnosed with idiopathic intracranial hypertension and 20 control participants were evaluated. Control subjects and patients were scanned with a 1.5 Tesla magnetic resonance imaging. Apparent diffusion coefficient maps were obtained from diffusion-weighted imaging with a b value of 1000 s/mm2 and apparent diffusion coefficient values were automatically calculated. These images were obtained by a radiologist who was blinded to the details of the study for center of each vitreous humor and the body of lateral ventricle. The mean apparent diffusion coefficient values of each vitreous humor and the body of the lateral ventricle were calculated for each group (control group and patients) and quantitative comparisons were performed. Results - There were no statistically significant differences in mean apparent diffusion coefficient values of the right vitreous humor, left vitreous humor and the body of the lateral ventricle between the patients with idiopathic intracranial hypertension and the control group (p=0.766, p=0.864, p=0.576, respectively). Discussion - Vitreous humor is a closed system and has no direct relationship with the cerebrospinal fluid or cerebral tissue and although morphological changes occur in the orbital structures, including the optic disk and optic nerve in idiopathic intracranial hypertension, the indirect effects of these changes on the vitreous humor may be too subtle to measure. Conclusion - We did not find a significant difference in the mean apparent diffusion coefficient value of the vitreous humor between the patients with idiopathic intracranial hypertension and the control group. However, future studies will be necessary to determine if changes in the vitreous humor can be used to diagnose intracranial hypertension.

Clinical Neuroscience

Unilateral thalamic infarction causing downward gaze palsy in a patient with uncorrected tetralogy of fallot: a case report

ANNUS Ádám, BENCSIK Krisztina, JÁRDÁNHÁZY Tamás, VÉCSEI László, KLIVÉNYI Péter

Introduction - Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart disease (CHD). Adults with surgically uncorrected forms of this condition are extremely rare, since operation is recommended in childhood to prevent cyanosis. Cyanotic CHD increases the risk of thromboembolic events. An endothelial dysfunction caused by chronic hypoxia and shear stress due to rheological alterations with a platelet dysfunction appear to be the explanation behind this finding. Paramedian thalamic infarction causing vertical gaze palsy without midbrain involvement is an infrequent finding. We report here a rare case of a patient with untreated TOF, who suffered a left-sided unilateral thalamic infarction presenting as downward gaze palsy and diplopia. Case presentation - A 44-year-old women complained of sudden onset diplopia and vertigo. Neurological examination revealed a downward gaze palsy with other symptoms related to a vertebrobasilar territory circulatory disturbance. The MRI scan revealed an acute infarction, 8 mm in diameter in the left medial thalamic region without midbrain involvement. Discussion - Adults with uncorrected forms of TOF are extremely uncommon, and descriptions of stroke in these patients are therefore rarities. We set out to give a concise survey of the literature regarding TOF patients with stroke. Conclusion - We present a rare case of unilateral thalamic infarction causing downward gaze palsy in an adult patient with uncorrected TOF. Cyanotic CHD is regarded as one of the risk factors of stroke. Besides other pathologic conditions, ischaemic stroke at an early age should raise the suspicion of a cardioembolic origin and, in rare cases, might result from cyanotic CHD.

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Clinical Neuroscience

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

JANSZKY József, HORVÁTH Réka, KOMOLY Sámuel

[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

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

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.

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

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.