Vagus Nerve Stimulation in the Treatment of Patients with Pharmacoresistant Epilepsy: Our Experiences

Vagus nerve stimulation (VNS) for the treatment of refractory partial epileptic seizures with or without secondary generalisation in patients older than 12 years was approved in Europe in 1994 and in the United States in 1997.We have studied the efficacy of VNS in patients with pharmacoresistant epilepsy hospitalized in the Neurology Department of the University Hospital Centre Zagreb. From 1997 do 2001 we have implanted VNS in 11 patients with pharmacoresistant epilepsy, who were magnetic resonance imaging (MRI) negative and from May 2007 to May 2009 in 11 patients with pharmacoresistant epilepsy, 9 of them were MRI positive, and were inoperable due to localisation of the pathomorphologic changes (ganglioglioma, hamartoma, various types of cortical dysplasia, porencephalic cysts), 2 were MR negative. In the group of MRI negative patients 1 patient had complex partial seizures (CPS), 6 patients had CPS with secondary generalisation, 2 patients had primary generalized epilepsy (PGE) including myoclonic, absence, atonic and tonic-clonic seizures, one patient had PGE and CPS, and 3 patients had Lennox-Gastaut syndrome (LGS). In the group of MRI positive patients one patient had elementary partial seizures (EPS) and CPS, two patients had EPS and CPS with secondary generalisation, one patient had CPS, 3 patients had CPS with secondary generalisation, and 2 patients had CPS with secondary generalisation as well as atonic seizures. After continuous follow-up of 11 MRI negative patients during 5 years and 2 MRI negative patients during one year there was decrease in mean-seizure frequency of 51.67%. After continuous follow-up of 9MRI positive patients during 2 years there was decrease in mean-seizure frequency of 61.9 %. The most frequent side effects were hoarseness, throat pain and cough in the »on phase« of the VNS, but they were mild and transitory. We can conclude that VNS was effectivemode of therapy in our group of patients with pharmacoresistant epilepsy

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

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)

Povezanost upalnih parametara i infekcija krvi uzrokovanih multirezistentnim Gram negativnim bakterijama kod COVID-19 pozitivnih bolesnika liječenih u jedinici intenzivnog liječenja – retrospektivna studija jednog centra

Objectives: During the COVID-19 pandemics we have seen in critically ill COVID-19 patients treated in the intensive care unit the parallel outbreak of multidrug resistant Gram-negative bacteria bloodstream infections, mainly Acinetobacter baumannii and Klebsiella pneumoniae. Methods: We conducted a retrospective cohort single-center study. The aim was to investigate the incidence, etiology and impact of intensive care unit bloodstream infections in COVID-19 patients admitted to the COVID-19 intensive care unit with a known burden of multidrug resistance and to evaluate the possibility that inflammatory parameters levels measured at two different time points of treatment can early predict multidrug resistant Gram-negative bacteria bloodstream infections and enable timely beginning of bacterial targeted antimicrobial therapy. Results: Our study confirmed that procalcitonin values of 2,46 mcg/L and neutrophil/lymphocyte ratio of 28,9 could be a reliable indicators for high risk stratification of multidrug resistant Gram-negative bacterial infection origin in critically ill COVID-19 patients (Mann Whitney U test, P=0,02). Conclusion: Monitoring dynamic shift of inflammatory parameters in critically ill COVID-19 patients could reliably help clinician to recognize the multidrug resistant Gram-negative bacteria bloodstream infections and start with the antimicrobial therapy in a timely manner.Cilj istraživanja: Tijekom COVID-19 pandemije uočili smo kod kritično bolesnih COVID-19 pozitivnih bolesnika liječenih na odjelu intenzivne njege paralelno izbijanje infekcija krvi uzrokovanih multirezistentnim Gram negativnim bakterijama, uglavnom Acinetobacter baumannii i Klebsiella pneumoniae. U praksi rezultati mikrobiološke potvrde infekcija krvi završeni su s određenom vremenskom odgodom. Stoga primarni cilj istraživanja bio je odrediti povezanost upalnih parametara (leukociti, limfociti, neutrofili, omjer neutrofila i limfocita, C-reaktivni protein, prokalcitonin) mjerenih u dvije različite vremenske točke (dan prijema u jedinicu intenzivnog liječenja i dan nastanka infekcija krvi potvrđenih pozitivnim hemokulturama) i nastanka infekcija krvi uzrokovanih multirezistentnim Gram negativnim. Sekundarni ciljevi istraživanja bili su istražiti učestalost, etiologiju i utjecaj infekcija krvi uzrokovanih multirezistentnim Gram negativnim bakterijama na ishod liječenja COVID-19 pozitivnih bolesnika. Materijali i metode: Proveli smo retrospektivno kohortno istraživanje u Kliničkoj bolnici Dubrava na intenzivističkom odjelu COVID-19 pozitivnih bolesnika u vremenskom period od 31. listopada 2020. godine do 31. ožujka 2021. godine. U istraživanju je sudjelovalo 166 COVID-19 pozitivnih bolesnika koji su zadovoljili kriterije uključenja u istraživanje. 122 COVID-19 bolesnika imali su mikrobiološki potvrđenu infekciju krvi uzrokovanu multirezistentnim Gram negativnim bakterijama. Kontrolna gupa imala je 44 COVID-19 bolesnika koji nisu razvili infekciju krvi. Svi podaci bolesnika skupljali su se iz povijesti bolesti i elektroničke baze podataka. Rezultati: Naša studija potvrdila je cut-off vrijednosti upalnih parametara prokalcitonina od 2,46 mcg/L i omjer neutrofila/limfocita od 28,9 kao pouzdane pokazatelje stratifikacije visoko rizičnih COVID-19 bolesnika za nastanak infekcije krvi uzrokovane multirezistentnim Gram negativnim bakterijama, Acinetobacter baumannii i Klebsiella pneumoniae (Mann Whitney U test, P=0,02). Zaključak: Dinamički monitoring upalnih parametara sa cut-off vrijednostima proklacitonina i omjera neutrofila i limfocita u različitim vremenskim intervalima u kritično bolesnih COVID-19 pozitivnih bolesnika pouzdani je pokazatelj visokog rizika nastanka infekcija krvi uzrokovanih multirezistentnim Gram negativnim bakterijama koji u kliničkoj praksi omogućuje pravovremeno uvođenje ciljane antimikrobne terapije prije dospijeća mikrobiološke potvrde

Vagus nerve stimulation in the treatment of patients with pharmacoresistant epilepsy: our experiences [Stimulacija vagusnog živca u liječenju bolesnika s farmakorezistentnom epilepsijom: naša iskustva]

Vagus nerve stimulation (VNS) for the treatment of refractory partial epileptic seizures with or without secondary generalisation in patients older than 12 years was approved in Europe in 1994 and in the United States in 1997. We have studied the efficacy of VNS in patients with pharmacoresistant epilepsy hospitalized in the Neurology Department of the University Hospital Centre Zagreb. From 1997 to 2001 we have implanted VNS in 11 patients with pharmacoresistant epilepsy, who were magnetic resonance imaging (MRI) negative and from May 2007 to May 2009 in 11 patients with pharmacoresistant epilepsy, 9 of them were MRI positive, and were inoperable due to localisation of the pathomorphologic changes (ganglioglioma, hamartoma, various types of cortical dysplasia, porencephalic cysts), 2 were MR negative. In the group of MRI negative patients 1 patient had complex partial seizures (CPS), 6 patients had CPS with secondary generalisation, 2 patients had primary generalized epilepsy (PGE) including myoclonic, absence, atonic and tonic-clonic seizures, one patient had PGE and CPS, and 3 patients had Lennox-Gastaut syndrome (LGS). In the group of MRI positive patients one patient had elementary partial seizures (EPS) and CPS, two patients had EPS and CPS with secondary generalisation, one patient had CPS, 3 patients had CPS with secondary generalisation, and 2 patients had CPS with secondary generalisation as well as atonic seizures. After continuous follow-up of 11 MRI negative patients during 5 years and 2 MRI negative patients during one year there was decrease in mean-seizure frequency of 51.67%. After continuous follow-up of 9 MRI positive patients during 2 years there was decrease in mean-seizure frequency of 61.9%. The most frequent side effects were hoarseness, throat pain and cough in the "on phase" of the VNS, but they were mild and transitory. We can conclude that VNS was effective mode of therapy in our group of patients with pharmacoresistant epilepsy