Seizure freedom with vagus nerve stimulation in neurofibromatosis type 1: A case report

Epileptic seizures in neurofibromatosis type 1 (NF1) have been a subject of investigation of numerous studies, however, their etiology has not yet been elucidated. They are usually well controlled with an- tiseizure medications (ASMs), but in some pharmacoresistant patients, vagus nerve stimulation (VNS) might present a complementary treatment modality. We present a 24-year-old male patient with NF1 who had temporal lobe seizures - focal autonomic seizures with impaired awareness and oroalimentary automatisms, as well as focal motor seizures with retained awareness, in addition to moderate intel- lectual disability. The most significant magnetic resonance (MRI) abnormalities included infiltrative changes of medulla oblongata, pons and cerebellum, as well as signal intensity changes with mild com- pression in the apex of the temporal lobes, insular cortex, putamen and medial part of the frontal lobe, all more prominent on the right, along with right mesial temporal sclerosis. Interictal electroencepha- logram (EEG) showed two independent epileptic foci – one in the right frontocentrotemporal region and the other in the left centrotemporal region. Throughout the years, he had been treated with several ASMs in monotherapy or polytherapy without success in seizure control. After an extensive preoperative evaluation, VNS implantation was performed and the patient has been seizure free for almost two years. Al- though a palliative intervention, VNS could be a powerful tool in the treatment of these patients and even lead to seizure freedom. To the best of our knowledge, this is the first case report where seizure freedom was achieved in a patient with NF1 following VNS implantation

SEXUAL DYSFUNCTION IN PATIENTS WITH EPILEPSY

Background: Patients with epilepsy commonly report sexual dysfunction (SD) and reproductive difficulties. This study aimed to evaluate the relationship between epilepsy, antiepileptic drugs (AEDs) and SD, and its association with the quality of life and depressive symptoms. Subjects and methods: This was a prospective study carried out in a tertiary healthcare centre. SD was evaluated using the internationally acclaimed questionnaire Arizona Sexual Experiences Scale (ASEX) that was successfully translated into Croatian and validated for this purpose. Depressive symptoms and quality of life were evaluated using the Hamilton Rating Scale for Depression (HAM-D17) and Quality of life in epilepsy-31 inventory (QOLIE-31). Results: Of 108 patients (68 (63 %) women, 40 (37 %) men, mean age 39.54±15.91 (range18-80) years) with epilepsy, 16 (14.8%) had focal, 38 (35.2%) generalized and 44 (40.7%) both types of epilepsy. Mean overall total score on the ASEX questionnaire was 11.94±5.61 (mean total score women 12.85±6.00, mean total score men 10.4±4.55), with 48 reporting that they had sexual activity in the past week. Nine (8.33%) patients (7 (6.48%) women, 2 (1.85%) men, mean age 47.66±19.33 (range 25-80) years) had a score 19 and above, 38 (35.18%) patients (27 (25%) women, 9 (8.33%) men, mean age 46.82±17.78 (range 19-80) years) individual score 5 and above on any one item, and 33 (30.55%) patients (26 (24.07%) women, 7 (6.48%) men, mean age 48.87±17.8 (range 19-80) years) had an individual score 4 and above on any three items. Significant correlations were found between SD and older age (p=0.001) and between more pronounced symptoms regarding SD on ASEX and female gender (p=0.000). There were no significant correlations between the type of epilepsy and SD, nor between the AEDs (old generation vs. modern) and SD. Significant correlations were found between the SD and more pronounced depressive symptoms (p=0.003) and between the SD and a lower quality of life (p=0.001). Conclusions: Results of our study suggest SD is experienced by around one-third of patients in our group, which is similar to the previous percentage of SD reported in the community sample. Women were found to experience more pronounced symptoms of SD on ASEX. Symptoms of SD were found to be significantly correlated with older age, female gender, lower quality of life and depressive symptoms, while no significant correlations were found with the type of epilepsy and the AEDs

DEPRESSION AND QUALITY OF LIFE IN PATIENTS WITH EPILEPSY - SINGLE CENTRE EXPERIENCE

Background: Patients with epilepsy commonly report depressive symptoms. The main aim of this study was to evaluate the relationship between epilepsy, antiepileptic drugs (AEDs) and depression. We also wanted to evaluate possible association between depressive symptofigms in patients with epilepsy with the quality of life (QoL). Material and methods: This was a prospective cross-sectional study carried out at the tertiary teaching hospital (University Hospital Centre Zagreb, Croatia) with Ethics committee approval. Questionnaires evaluating depressive symptoms and QoL were administered to consecutive patients treated in the Referral Centre of the Ministry of Health of the Republic of Croatia for Epilepsy. Depressive symptoms were evaluated using Hamilton Rating Scale for Depression (HAM-D17). Quality of life was assessed using Quality of life in epilepsy-31 inventory (QOLIE-31) Results: 108 patients (63% women, 37% men; mean age 39.54±15.91 years, range 18-80 years) with epilepsy were included. 14.8% of patients had focal, 35.2% generalised and 40.7% both types of epilepsy. Majority of patients (65.74%) were on two and more AEDs and quarter was on monotherapy (25%); 42% were on newer, 19% on older and 39% on both AEDs. Mean total score on HAM-D17 was 9.94±8.18 (men - mean total score 10.16±8.85, women - mean total score 9.81±7.84). There were no significant differences on HAM- newer AEDs, or both types AEDs) and results on HAM-D17, nor between the type of epilepsy and results on HAM-D17. We found strong negative correlation between the higher QoL and HAM-D17 (p=0.000). Conclusions: Results of this study evaluating depressive symptoms in patients with epilepsy demonstrate that our patients mainly experience mild depressive symptoms, with no significant differences on HAM-D17 regarding gender and age. Patients with epilepsy with less pronounced depressive symptoms were found to have higher QoL. We did not find statistically significant differences regarding the type of epilepsy and results on HAM-D17, nor between the AEDs (older vs. newer AEDs, or both types AEDs) and results on HAM-D17

Kvaliteta života bolesnika s epilepsijom - naša iskustva

A prospective study was carried out at the Zagreb University Hospital Centre to evaluate the relationship between epilepsy, antiepileptic drugs (AEDs) and quality of life (QoL) in patients with epilepsy (PE), and its association with depressive symptoms and sexual dysfunction (SD). QoL was assessed by use of the Quality of Life in Epilepsy-31 Inventory (QOLIE-31), SD by the Arizona Sexual Experiences Scale (ASEX), and depressive symptoms by the Hamilton Rating Scale for Depression (HAM-D17). The study included 108 PE (women 63% and men 37% men), mean age 39.54±15.91 years. Focal type epilepsy was diagnosed in 14.8%, generalized type in 35.2%, and both types were present in 40.7% of study patients. Drug-resistant epilepsy (DRE) was present in 44/108 and vagus nerve stimulation (VNS) was implanted in 27/44 patients. The mean response on QOLIE-31 was 62.88±17.21 with no significant differences according to gender, type of epilepsy, and age. A statistically significantly lower QoL was found in the ‘Overall QoL’ domain (35-55 vs. <35 age group). Patients taking both types of AEDs had a significantly lower QoL compared to those on newer types of AEDs. Higher QoL was associated with less pronounced depressive symptoms (p=0.000). Significant correlations were found between lower QoL and SD (p=0.001). In 27 patients with DRE having undergone VNS, a favorable effect of VNS implantation on the QoL and mood was observed as compared with 18 patients without VNS (p=0.041).Provedeno je prospektivno istraživanje u KBC-u Zagreb s ciljem procjene povezanosti epilepsije, antiepileptičkih lijekova (antiepileptic drug, AED) i kvalitete života (quality of life, QoL) u bolesnika s epilepsijom, kao i učestalosti depresije i seksualne disfunkcije (SD). QOLIE-31 (Quality of Life in Epilepsy-31 Inventory) je primijenjen za procjenu QoL-a, ASEX (Arizona Sexual Experiences Scale) za SD i HAM-D17 (Hamilton Rating Scale) za depresiju. Uključeno je 108 bolesnika s epilepsijom (63% žena, 37% muškaraca; srednja dob 39,54±15,91 godina). Žarišnu epilepsiju imalo je 14,8% i generaliziranu 35,2% bolesnika, dok je obje vrste epilepsije imalo 40,7% bolesnika. Farmakorezistentnu epilepsiju (drug-resistant epilepsy, DRE) imalo je 44/108 bolesnika, a kod njih 27/44 ugrađen je stimulator vagusnog živca (vagus nerve stimulation, VNS). Srednji odgovor na QOLIE-31 bio je 62,88±7,21 bez značajnih razlika u odnosu na spol, vrstu epilepsije i dob. Statistički značajno niži QoL nađen je u domeni ‘Sveukupni QoL’ (dobna skupina 35-55 godina u odnosu na dobnu skupinu <35). Bolesnici koji su uzimali obje vrste AED imali su značajno niži QoL u usporedbi s onima na novijim AED. Viši QoL bio je povezan s manje izraženim simptomima depresije (p=0,000). Pronađene su značajne korelacije između nižeg QoL-a i SD (p=0,001). U bolesnika s DRE utvrđen je pozitivan utjecaj ugradnje VNS-a na QoL i raspoloženje (27 bolesnika s VNS-om u usporedbi s 18 bolesnika bez VNS-a, p=0,041)

The importance of postprocessing magnetic resonance imaging of the brain in preoperative diagnosis of patients with pharmacoresistant epilepsy

Uvod: Epilepsija je kronična bolest središnjeg živčanog sustava koja se javlja u 1% populacije. Kod velikog broja bolesnika se pravilnim odabirom antiepileptičkih lijekova može postići zadovoljavajuća kontrola napadaja, dok preostalih 25-35% ima farmakorezistentnu epilepsiju i smatra se kandidatima za neurokirurško liječenje. Prijeoperacijska obrada bolesnika s farmakorezistentnom epilepsijom obuhvaća različite neinvazivne i invazivne metode. Najznačajniji neuroradiološki postupak u pravilnom odabiru kandidata pogodnih za neurokirurgiju je MR mozga 3T (magnetska rezonancija). Postprocesiranje snimki MR mozga s MAP07 morfometrijskom analizom (Morphometric Analysis Program) je sofisticirani dijagnostički postupak. Program nudi brojne grafičke prikaze kroz tri statističke mape i olakšava detekciju i lokaliziranje skleroze hipokampusa, žarišne kortikalne displazije i drugih vrsta kortikalnih malformacija, koje se ne mogu lako otkriti konvencionalnom vizualnom analizom MR-a. ----- Ispitanici i metode: U istraživanju je sudjelovalo 120 bolesnika s farmakorezistentom epilepsijom, starijih od 16 godina. MR mozga 3T učinjen je u skladu s dizajniranim MR protokolom za obradu epilepsije, nakon čega su prikupljeni podaci i učinjena naknadna obrada MR snimaka u potpuno automatiziranom MATLAB skriptu (engl. MATrix LABoratory), MAP07 morfometrijskoj analizi, primjenom algoritama SPM5 (engl. Statistical Parametric Mapping). ----- Rezultati: Analiza na našim bolesnicima pokazala je visoku osjetljivost MAP07 mofrometrijske analize s niskom specifičnošću i s velikim udjelom lažno pozitivnih bolesnika. Nakon MR analize, 32/120 bolesnika označeno je kao MR negativno. Kod navedenih bolesnika je nakon MAP07 analize utvrđeno 5 strukturnih lezija, kod jednog bolesnika hipokampalna skleroza (HS), kod jednog fokalna kortikalna displazija (FCD), kod dvoje perinatalne vaskularne lezije i u jednog bolesnika hiperintenzitet hipokampusa. Nađena je visoka sveukupna podudarnost nalaza MAP07 morfometrijske analize i MR za otkrivanje FCD, HS, perinatalne ishemije / kronične vaskularne lezije, heterotopije i polimikrogirije (koeficijent kappa iznad 0,700). ----- Zaključak: MAP07 morfometrijska analiza je korisna, automatizirana metoda koja može voditi dodatnu ponovnu re-evaluaciju MR nalaza, isticanjem suspektnih kortikalnih regija, te može poslužiti kao komplementarna metoda konvencionalnim vizualnim MR analizama poboljšavanjem vizualizacije malformacija kortikalnog razvoja.Background: Epilepsy is a chronic disease of the central nervous system that affects 1% of the population. The large number of patients with the proper selection of antiepileptic drugs can achieve satisfactory seizure control, while the remaining 25-35% have pharmacoresistant epilepsy and are considered as candidates for active neurosurgical treatment. Preoperative evaluation of patients with pharmacoresistant epilepsy encompasses non-invasive and invasive methods, were brain MRI (Magnetic resonance imaging) is crucial in delineation of structural lesions. The most significant neuroradiological procedure in proper selection of candidates suitable for neurosurgery is brain MRI 3T. Post-processing of brain MRI with MAP07 (Morphometric Analysis Program) is a sophisticated diagnostic procedure. The program offers a number of graphical post-processing methods (maps) and facilitates the detection and localization of hippocampal sclerosis, focal cortical dysplasias and other types of cortical malformations, which cannot be easily detected by conventional neuroradiological methods. ----- Subjects and methods: 120 patients with epilepsy have been recruited due to pharmacoresistant epilepsy, aged > 16 yrs. MRI 3T was performed according to designes epilepsy imaging protocol followed by data acquisition and postprocessing of MRI data in fully automated MATLAB script (MATrix LABoratory), MAP07, by applying SPM5 algorithms (engl. Statistical Parametric Mapping). ----- Results: Analysis in our patients, showed high sensitivity of MAP07 with low specificity. and with a high proportion of false-positive patients. After MRI analysis, 32/120 patients were labeled as MRI negative, in whom after MAP07 analysis in 5 patients structural lesions were found, in one hippocampal sclerosis (HS), in one focal cortical dysplasia (FCD), in two perinatal vascular lesions and in one hippocampal hyperintensity. There was quite high overall coincidence of the findings of MAP07 and MRI for detection of FCD, HS, perinatal ischaemia/chronic vascular lesions, heterotopia and polymicrogyria (kappa coefficient above 0.700). ----- Conclusions: MAP07 analysis is a useful, automated method that may guide additional re-evaluation of MRI by highlighting suspeciuos cortical regions, as a complementary method to conventional visual MRI analysis by enhancing the visualization of malformation of cortical development

Brain MRI post-processing with MAP07 in the preoperative evaluation of patients with pharmacoresistant epilepsy – Croatian single centre experience

Objective: This study aimed to determine the role of brain MRI post-processing method MAP07 (Morphometric Analysis Program) in detecting epileptogenic brain lesions in patients with pharmacoresistant epilepsy (PE). MAP07 is a sophisticated diagnostic program that offers several morphometric maps and facilitates the detection and localization of hippocampal sclerosis (HS), focal cortical dysplasias (FCD), and other types of cortical malformations, which could be undetected by conventional visual MRI analysis (CVA). ----- Methods: 120 patients aged > 16 years with PE have been recruited. 3 T MRI was performed according to epilepsy imaging protocol followed by image postprocessing with a fully automated MATLAB script, MAP07, by applying SPM5 algorithms. Statistical analysis was performed in IBM SPSS Statistics, version 25.0. ----- Results: Analysis in our patients showed a high sensitivity of MAP07 with low specificity and with a high proportion of false-positive patients. After MRI analysis, out of 120 patients, 32 were found to have no structural abnormalities by conventional visual analysis in whom after MAP07 in 5 patients structural lesions were found (in one HS, in one FCD, in two perinatal vascular lesions, and in one hippocampal hyperintensity). There was a quite high overall coincidence of the findings of MAP07 and MRI for the detection of FCD, HS, perinatal ischemia/chronic vascular lesions, heterotopias, and polymicrogyria (kappa coefficient above 0.700). ----- Conclusions: MAP07 analysis is a useful, additional, and automated method that may guide re-evaluation of MRI by highlighting suspicious cortical regions, as a complementary method to CVA, by enhancing the visualization of cortical malformations and lesions