Clinical Neuroscience

[EFFECTS OF ANTIEPILEPTIC DRUGS ON MOOD OF PEOPLE WITH EPILEPSY]

RAJNA Péter

SEPTEMBER 30, 2007

Clinical Neuroscience - 2007;60(09-10)

[This article deals with the effect of antiepileptic drugs on mood when applied in epiletic patients. The author points that depressive symptoms occur significantly more frequently in epilepsy and there are more common factor in the mechanism of action of the antiepileptic and antidepressive agents. The relevant literature is surprisingly poor. Primary and large analysis regarding affective disorders coexisting with epilepsy is still lacking. From this aspect some antiepileptic drugs have not been investigated at all. The consequences of the papers originates from indirect sources like adverse events profiles of the study drugs or from psychometric tests performed for avoiding exclusion criteria of psychological nature. On the other hand the paper deals also with the difficulties of such kind of investigations concerning the classification of depressive signs presenting with epilepsy, special considerations of inclusion of appropriate patients and particular limits of the measuring and follow-up of the observed effect. As the result of the detailed analysis of the literature the author recommends lamotrigine, carbamazepine and oxcarbazepine as first choice antiepileptic drug for epileptic patients suffering from depressive disorder, too. On the contrary, phenobarbital, topiramate and vigabatrin are able to worsen the affective symptoms. Aimed, randomized, controlled studies are necessary for recognizing the whole spectrum of psychotropic effects of antiepileptic drugs and for their successful and individually tailored application in patients in their comorbide states. Author calls the attention for the importance of the treatment of depressive states frequently occurring in epileptic patients. These symptoms modify the compliance of the patients and are able to influence even the epileptic process itself.]

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Clinical Neuroscience

[PERSISTENT AKINETIC-RIGID SIDE EFFECTS OF NEUROLEPTICS MAY INDICATE WILSON'S DISEASE]

ASCHERMANN Zsuzsanna, SZALAY Ferenc, SCHMIDT Erzsébet, KOMOLY Sámuel, ILLÉS Zsolt

[Here we report two cases, where neuroleptic treatment provoked persistent akinetic-rigid symptoms resulting in the diagnosis of Wilson's disease. No liver function abnormalities suggested Wilson's disease in one of the cases. In both cases, the akinetic-rigid symptoms were originally attributed to side effects of neuroleptics, but symptoms persisted after discontinuation of treatment. In one of the cases, T2-weighted cranial MRI indicated bilateral hyperintense signals in the basal ganglia. Our cases suggest that in a subgroup of Wilson's disease, dopamin receptor antagonists may provoke akinetic-rigid neurological symptoms possibly due to the damage of dopaminergic neurons. Persistent akinetic-rigid side effects of neuroleptics in young patients thus require diagnostic tests to exclude Wilson's disease even in unsuspected cases.]

Clinical Neuroscience

[POSSIBLE ROLE OF THE BASAL GANGLIA IN THE GENERATION OF THE N30 POTENTIAL OF THE MEDIAN NERVE SOMATOSENSORY EVOKED POTENTIALS]

BENICZKY Sándor, NAGY Helga, VARGA Edina, VÖRÖS Erika, KÉRI Szabolcs, VÉCSEI László

[Background and purpose - The origin and afferentation of the frontal N30 component of the median nerve somatosensory evoked potentials (SEPs) have not yet been fully elucidated. The aim of this study was to assess the possible selective impairment of the N30 component in patients with lacunar infarcts of the basal ganglia as compared to patients with lacunar infarctions sparing the basal ganglia and to a group of healthy subjects. Methods - Median nerve SEPs were measured in ten patients with lacunar infarctions of the brain (but no cortical atrophy or leukoaraiosis) and 13 healthy volunteers. Four patients had lacunar infarctions affecting the basal ganglia and 6 patients had lesions affecting other structures. Results - In two patients with lesions affecting the head of the caudate nucleus, there was no identifiable N30 component on the affected side. In one patient with bilateral lesions of the globus pallidus, the amplitude of the N30 component was significantly reduced. In one patient with lesion of the tail of the caudate nucleus, the N30 component was unaffected. The amplitude of the N30 component was also reduced in two patients with frontal subcortical white matter lesions. In all the other subjects, we recorded normal N30 components on both sides. Conclusion - Our results further support the importance of the basal ganglia, especially the head of the caudate nucleus in the generation of the N30 component of the median nerve SEPs.]

Clinical Neuroscience

[ANIMAL MODELS OF CEREBRAL ISCHEMIA - TESTING THERAPEUTIC STRATEGIES IN VIVO]

ERDŐ Franciska, KONSTANTIN-ALEXANDER Hossmann

[Acute cerebral ischemia is one of the leading causes of mortality and chronic disability worldwide. Animal models of focal (stroke-type) and global (cardiac arrest-type) ischemia have been established to investigate the morphological, functional and molecular consequences and to design therapeutic strategies for the improvement of ischemic injury. Despite highly beneficial effects in experimental studies, most human clinical trials were disappointing, suggesting inefficacies in the design and/or translation of animal experiments. In this review the pathophysiologically relevant particularities of ischemia models will be discussed to provide a rational basis for the proper selection of animal models for testing therapeutic strategies under experimental conditions.]

Clinical Neuroscience

[IDIOPATHIC NOCTURNAL FRONTAL LOBE EPILEPSY - AN UNUSUAL EPILEPSY SYNDROME]

HALÁSZ Péter, SZŰCS Anna, KELEMEN Anna

[This paper provides an overview of the development of conceptions about nocturnal frontal lobe epilepsy syndrome and describes the electro-clinical characteristics, the identity of the genetic and sporadic variant, and the relationship of the EEG and clinical signs with NREM sleep specific features. The differential diagnostic difficulties and open questions on the pathomechanism are emphasized especially in relation with the lack of epileptiform EEG signs, circumsribed seizure onset zone and cognitive deficits. The relationship of frontal automatisms and NREM parasomnias are also discussed in relation of the place of nocturnal frontal lobe epilepsy among other epilepsies.]

Clinical Neuroscience

[SIMULTANEOUS CENTRAL AND PERIPHERAL NERVOUS SYSTEM INVOLVEMENT IN SYSTEMIC LUPUS ERYTHEMATOSUS]

ILNICZKY Sándor, KAMONDI Anita, ARÁNYI Zsuzsanna, VÁRALLYAY György, GAAL Barbara, SZIRMAI Imre, NAGY György

[Systemic lupus erythematosus is a frequent autoimmune disease, affecting several organs, including the brain, spinal cord and nerves. Cerebral vasculitis, transverse myelitis and polyneuropathy are the most common neurological manifestations. We report a case of a 46 years old woman who suffered incomplete transverse myelitis in her age of 44. After 2 years the second relapse presented with arthralgias, painful paraesthesias and weakness of the lower limbs. Neurological signs suggested involvement of the central and the peripheral nervous system. Based upon clinical and laboratory findings systemic lupus erythematosus was diagnosed. Magnetic resonance imaging revealed two hyperintense lesions on T2 weighted scans within the cervical spinal cord. The brain scan was normal. Protein content was slightly elevated in the cerebrospinal fluid, with normal cell count. Electrophysiological examinations diagnosed a subacute sensory-motor axonal polyneuropathy. On methylprednisolone treatment her condition improved. Simultaneous development of central and peripheral lesions of the nervous system in cases with systemic lupus erythematosus may lead to a challenge to establish the diagnosis.]

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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

Validation of the Hungarian PHQ-15. A latent variable approach

STAUDER Adrienne, WITTHÖFT Michael, KÖTELES Ferenc

Somatic symptoms without a clear-cut organic or biomedical background, also called “medically unexplained” or “somatoform” symptoms, are frequent in primary and secondary health care. They are often accompanied by depression and/or anxiety, and cause functional impairment. The Patient Health Question­naire Somatic Symptom Scale (PHQ-15) was developed to measure somatic symptom distress based on the frequency and bothersomeness of non-specific somatic symptoms. The study aimed to (1) evaluate the Hungarian version of the PHQ-15 from a psychometric point of view; (2) replicate the bifactor structure and associations with negative affect described in the literature; and (3) provide the Hungarian clinical and scientific community with reference (normal) values split by sex and age groups. PHQ-15, depression (BDI-R), and subjective well-being (WHO-5) scores obtained from a large (n = 5020) and close to representative community sample (Hun­garostudy 2006) were subjected to correlation analysis and linear structural equation modeling. The PHQ-15 showed good internal consistency (Cronbach’s α = 0.810; McDonald’s ω = 0.819) and moderate to strong correlation with the BDI-R (rs = .49, p < 0.001) and WHO-5 (rs = -.48, p < 0.001). Fit of the bifactor structure was excellent; in independent analyses, the general factor was strongly associated with depression (β = 0.656±0.017, p < 0.001) and well-being (β = -0.575±0.015, p < 0.001), whereas the symptom specific factors were only weakly or not related to these constructs. The PHQ-15 score was higher in females and showed a weak positive association with age. The Hungarian PHQ-15 is a psychometrically sound scale which is positively associated with depression and ne­gatively related to subjective well-being. The bifactor structure indicates the existence and meaningfulness of a gene­ral factor representing the affective-motivational component of somatic symptom distress. The Hungarian version of the PHQ-15 is a brief and usable tool for the pre-screening of somatization disorder (DSM-IV) or somatic symptom disorder (DSM-5). The reported reference values can be used in the future for both clinical and research purposes.

Clinical Neuroscience

Management of bone metabolism in epilepsy

UÇAN TOKUÇ Ezgi Firdevs , FATMA Genç, ABIDIN Erdal, YASEMIN Biçer Gömceli

Many systemic problems arise due to the side effects of antiepileptic drugs (AEDs) used in epilepsy patients. Among these adverse effects are low bone mineral density and increased fracture risk due to long-term AED use. Although various studies have supported this association with increased risk in recent years, the length of this process has not been precisely defined and there is no clear consensus on bone density scanning, intervals of screening, and the subject of calcium and vitamin D supplementation. In this study, in accordance with the most current recommendations, our applications and data, including the detection of possible bone mineralization disorders, treatment methods, and recommendations to prevent bone mineralization disorders, were evaluated in epilepsy patients who were followed up at our outpatient clinic. It was aimed to draw attention to the significance of management of bone metabolism carried out with appropriate protocols. Epilepsy patients were followed up at the Antalya Training and Research Hospital Department of Neurology, Epilepsy Outpatient Clinic who were at high risk for osteoporosis (use of valproic acid [VPA] and enzyme-inducing drugs, using any AED for over 5 years, and postmenopausal women) and were evaluated using a screening protocol. According to this protocol, a total of 190 patients suspected of osteoporosis risk were retrospectively evaluated. Four patients were excluded from the study due to secondary osteoporosis. Of the 186 patients who were included in the study, 97 (52.2%) were women and 89 (47.8%) were men. Prevalence of low bone mineral density (BMD) was 42%, in which osteoporosis was detected in 11.8% and osteopenia in 30.6% of the patients. Osteoporosis rate was higher at the young age group (18-45) and this difference was statistically significant (p=0.018). There was no significant difference between male and female sexes according to osteoporosis and osteopenia rates. Patients receiving polytherapy had higher osteoporosis rate and lower BMD compared to patients receiving monotherapy. Comparison of separate drug groups according to osteoporosis rate revealed that osteoporosis rate was highest in patient groups using VPA+ carbamazepine (CBZ) (29.4%) and VPA polytherapy (19.4%). Total of osteopenia and osteoporosis, or low BMD, was highest in VPA polytherapy (VPA+ non-enzyme-inducing AED [NEID]) and CBZ polytherapy (CBZ+NEID) groups, with rates of 58.3% and 55.1%, respectively. In addition, there was no significant difference between drug groups according to bone metabolism markers, vitamin D levels, and osteopenia-osteoporosis rates. Assuming bone health will be affected at an early age in epilepsy patients, providing lifestyle and diet recommendations, avoiding polytherapy including VPA and CBZ when possible, and evaluating bone metabolism at regular intervals are actions that should be applied in routine practice.

Clinical Neuroscience

[Personalised epilepsy treatment]

ALTMANN Anna

[Epilepsy is one of the most common chronic neurological disease in childhood. Patients with epilepsy – even with so-called benign epilepsy – need medication for years. During this time, children go through a very big change, not only gaining weight and height, but also changing hormonal and metabolic processes. Maturation processes in different brain areas also take place at different rates depending on age. All of these should be considered when preparing a therapeutic plan. In everyday practice after the diagnosis of epilepsy, the applied drug is most often selected based on the shape and type of seizure. However, a number of other factors need to be considered when designing a therapeutic strategy: 1. efficacy (form of epilepsy, type of seizure), 2. age, gender, 3. pharmacological properties of the drug, 4. adverse drug reaction profile, 5. lifestyle (community), figure (skinny, corpulent, obese), 6. other comorbidities (nutrition, behavioral and learning problems, circulatory disorders, kidney or liver disease), 7. expected interactions with other drugs already used, 8. genetics, 9. other aspects (drug registration and prescription rules). The purpose of this article is to help to decide which antiepileptic drugs are expected to have the least side effects in a particular child with different comorbidities and which medications should be avoided if possible.]

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. ]