Snježana Miškov

Transplacental genotoxicity of antiepileptic drugs: animal model and pilot study on mother/newborn cohort.

Antiepileptic drugs (AED) as transplacental agents are known to have adverse effects on fetal development. Genotoxicity of AEDs is still not fully understood. The aim of present study was to investigate the transplacental genotoxicity of valproate on animal model and in 21 mothers and their newborns receiving AED. In both studies, in vivo micronucleus (MN) assay was used. Pregnant dams were exposed to Na-valproate (100mg/kg) on gestational days 12-14. Dams and pups receiving Na-valproate showed a significantly increased MN frequency (5.17 ± 1.17/1000; 5.20 ± 1.48/1000) compared to the control (1.0 ± 0.58/1000; 1.67 ± 1.03/1000). In mother/newborn study a significant increase of MN frequency was detected in newborns of mothers taking AEDs (3.09 ± 0.49/10,000) compared to the referent newborns (1.56 ± 0.22/10,000). The results of this study suggest that AEDs may act as transplacental genotoxins. Launching the mother/newborn cohorts for genotoxicological monitoring may give a significant new insight in health effects of AEDs.

Differences of blink-reflex abnormalities in patients suffering from idiopathic and symptomatic trigeminal neuralgia

SummaryWe investigated the brainstem blink reflex in patients suffering from idiopathic and symptomatic trigeminal neuralgia to establish possible dysfunction in the reflex cycle and determine eventual differences between the two disease types. The study included 35 patients with idiopathic disease and seven patients with symptomatic disease, their results compared with those of 50 normal controls. We stimulated the forehead afferents of the supraorbital nerve and recorded the response from both orbicularis oculi muscles. We tested latencies of bilateral late components (R2, R2′), irritative R3 component and the incidence of R3 component. The patients with idiopathic trigeminal neuralgia showed normal parameters of blink reflex, except for the greater incidence of R3 component. Patients with symptomatic trigeminal neuralgia showed prolonged latencies of R2, R2′ and R3 components when stimulating the afflicted side, but no significant difference in incidence of R3 component compared with the control group. The results indicate that abnormalities of blink reflex are significantly different in the two groups of patients. The high incidence of R3 component seems to be typical of idiopathic disease, whereas the prolonged latencies of late reflex components after stimulation of the afflicted side seem to be typical for symptomatic disease. These results suggest that testing the blink reflex may prove a significant aid in distinguishing the idiopathic and symptomatic disease types.ZusammenfassungWir untersuchten den Blinkreflex bei Patienten, die an einer idiopathischen bzw. einer symptomatischen Trigeminusneuralgie litten, um mögliche Funktionsstörungen im Reflexzyklus zu erfassen und um einen eventuellen Unterschied zwischen den Gruppen zu erheben. Untersucht wurden 35 Patienten mit idiopathischer und 7 Patienten mit symptomatischer Trigeminusneuralgie, verglichen mit einer Gruppe von 50 Kontrollpersonen. Nach elektrischer Stimulation an Foramen supraorbitale wurde die Reizantwort an beiden Mm. orbicularis oculi abgeleitet. Dabei wurden die Latenz der bilateralen späten Komponenten (R2, R2′) und der irritativen R3-Komponente sowie die Inzidenz der R3-Komponente gemessen. Die Patienten mit idiopathischer Trigeminusneuralgie zeigten bis auf eine höhere Inzidenz der R3-Komponente normale Parameter des Blinkreflexes. Die Patienten mit symptomatischer Trigeminusneuralgie wiesen im Vergleich zur Kontrollgruppe verlängerte Latenzen der R2-, R2′- und R3-Komponenten auf. Die Inzidenz der R3-Komponente zeigte keinen Unterschied zu Kontrollgruppe. Wir schließen aus unseren Ergebnissen, dass der Blinkreflex bei Trigeminusneuralgie je nach Erscheinungsform unterschiedlich beeinträchtigt ist. Eine hohe Inzidenz von R3-Komponenten scheint typisch für die idiopathische Form zu sein. Verlängerte Latenzzeiten der späten Reflexkomponenten nach Stimulation scheinen dahingegen typisch für die symptomatische Form der Erkrankung. Die Untersuchung des Blinkreflexes könnte daher zusätzliche Information für die Unterscheidung zwischen symptomatischer und idiopathischer Trigeminusneuralgie bieten.

Diagnostic value of some less frequently considered blink reflex parameters in idiopathic trigeminal neuralgia

ZusammenfassungZIEL DER STUDIE: Wir untersuchten den Wert von einigen weniger beachteten Blink-Reflex Parametern bei der Erstellung der Diagnose der idiopathischen Trigeminus Neuralgie. PATIENTEN: Die Studie wurde an 50 Patienten durchgeführt, die an einer idiopathischen Trigeminus Neuralgie, ohne andere erkennbare Erkrankung, litten, wobei die Diagnose nach den Richtlinien der internationalen Klassifikation von Kopfschmerz Erkrankungen gestellt worden war. METHODEN: Wir stimulierten den N. supraorbitalis an der Stirn (Foramen N. supraorbitalis) und zeichneten die Reflexantwort an beiden Mm orbicularis oculi auf. Das Auftreten folgender Ergebnisse wurde bestimmt: 1) Auftreten der ipsilateralen R3 Komponente, 2) Verlängerte Dauer (>25 ms)der R2 bei Stimulation an der befallenen Seite, 3) Auftreten der R1 Komponente während der Stimulation des kontralateralen N. supraorbitalis. Wir verglichen die Ergebnisse mit Werten, die bei 50 gesunden Personen der Kontrollgruppe erhoben wurden (Chisquare, p < 0.05). Es wurde die Sensitivität, die Spezifität und der diagnostische Wert der einzelnen Parameter bestimmt. ERGEBNISSE UND SCHLUSSFOLGERUNGEN: Alle drei untersuchten Parameter traten signifikant häufiger bei den erkrankten Personen auf als bei den Kontrollen. Das Vorkommen der R3 Komponente an der befallenen Seite hatte den höchsten diagnostischen Wert. Wir glauben, dass die erhobenen Ergebnisse eine elektrophysiologische Bestätigung der klinisch gestellten Diagnose einer idiopathischen Trigeminus Neuralgie geben können.SummaryAIM OF THE STUDY: We have done a study investigating the value of some less frequently considered Blink reflex parameters for establishing the diagnosis of idiopathic trigeminal neuralgia. PATIENTS: The study was done on 50 patients suffering from idiopathic trigeminal neuralgia, diagnosed according to the guidelines of the International Classification of Headache Disorders, with no other apparent illness. METHODS: We have stimulated the supraorbital nerve at the forehead (foramen n. supraorbitalis) and recorded the reflex response on both mm. orbiculares oculi. Incidence of following findings was determined: (1) occurrence of ipsilateral R3 component, (2) prolonged duration (>25 ms) of R2 when stimulating the affected side and (3) occurrence of R1 component during the stimulation of contralateral supraorbital nerve. We have compared these findings to those of 50 healthy subjects from the control group (Chi-square, p < 0.05). Sensitivity, specificity and diagnostic value for individual parameters were determined. RESULTS AND CONCLUSION: All three parameters tested proved to have a significantly higher incidence in the group of subjects. The occurrence of R3 component on the affected side showed the highest diagnostic value. Significance: We believe these findings could electrophysiologically reinforce the clinically established diagnosis of idiopathic trigeminal neuralgia.

Liposarcoma concurrence in a multiple sclerosis patient treated with interferon-beta 1b.

Patient self-reporting of adverse events is alternative approach and could provide valuable information. Data obtained from patients could be sometimes different from physicians but they are complementary, each providing clinically meaningful information. In this article we present a patient who has been suffering from multiple sclerosis, treated by Interferon Beta -1b (IFNB-1b) over the past 10 years. This self reported case of liposarcoma is suspected to be related to the concurrent treatment with IFNB-1b opens numerous questions. On the basis of data available yet, we cannot conclude that the use of IFNB - 1b is related with the occurrence of malign disease in this case, but our effort to communicate these concerns with the patient resulted in continuation of our co-operation with the patient and his willingness to continue with the same immunomodulatory agent. Relationship with patients based on mutual appreciation is crucial for compliance and prevention of future relapses of MS.

HRVATSKI MODEL INTEGRATIVNE PROSPEKTIVNE SKRBI TRUDNOĆA U ŽENA S EPILEPSIJOM

Epilepsy is the most common neurological complication in pregnancy. Women with epilepsy have a higher risk of complications in pregnancy. In Croatia, women with epilepsy are treated by neurologists at tertiary centers according to the place of residence. We prospectively followed-up pregnancies in women with epilepsy and healthy controls, and analyzed the factors responsible for their delivery outcomes and development of their babies. Healthy pregnant women had a higher level of education and economic status, but pregnant women with epilepsy took folic acid in a higher proportion than controls, possibly due to timely preconception counseling. Complications during pregnancy depended on the number of antiepileptic drugs and epilepsy control. We noticed some behavioral and cognitive aspects in children exposed in utero to valproic acid, which required follow up. The rate of congenital malformations was not increased. In conclusion, women with epilepsy should receive preconception counseling about the risk for pregnancy, but also about the possibilities to minimize that risk. We have introduced a model of integrative management of pregnancy and epilepsy based on close collaboration among different clinical experts in Croatia, in order to provide prompt counseling and timely intervention.

PO18-WE-45 Surveillance of Croatian pregnant women with epilepsy and effects of antiepileptic drugs exposure in their offspring

Purpose: The aim of the study was to evaluate the efficacy of alternative drugs when first-line valproic acid (VPA) fails in juvenile myoclonic epilepsy (JME). Material: 23 patients with JME in whom seizure control was insufficient (13) or experienced side effects (10) on VPA, were started with different drugs according to patient-specific variables. In three patients with only persistent myoclonias, clonazepam was added. In patients with uncontrolled myoclonias and tonic-clonic seizures we introduced: lamotrigine (LTG) in 10, topiramate (TPM) in 3, levetiracetam (LEV) in 3 and phenobarbital (PB) in 4 of them. Observational period was 6 months. Results: CNZ was effective in all 3 patients in suppressing myoclonias. In LTG group one patient drop out because of rush and another because of worsening of tremor when LTG added to VPA. Of remaining 8 patients, 3 were seizure free and in 2 marked reductions occurred. Worsening was observed in 2 and 1 without effect. TPM was effective in 1, LEV in 2 and PB in 2 of patients. Conclusion: In JME patients, in whom VPA failed, LTG, LEV and TPM of newer AEDs, but not to forget CNZ and PB in selected patients, could be useful therapeutic agents.

Gender differences in epilepsy.

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14 Surveillance of Croatian pregnant women with epilepsy and effects of antiepileptic drugs exposure in their offspring

characteristic for different pathological white matter processes. Conclusion: MRI is a very sensitive but unfortunately relatively unspecific method for evaluation of WML. As mentioned earlier, differential diagnosis of WML is a long list. Due to that the diagnosis of a specific pathological process characterised by one or more lesions in the white matter has to be made by combining clinical aspect and radiological assessment.