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-D17 regarding gender and age. We didn't find statistically significant differences regarding AEDs (older vs. 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.

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.

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.

Predictors of Quality of Life in Patients with Drug Resistant Epilepsy after Neurosurgical Treatment: One-Year Follow-Up.

BACKGROUND: Invasive neurosurgical treatment or minimally invasive neurosurgical treatment are methods of choice for the treatment of patients with drug resistant epilepsy. The aim of this study was to evaluate the impact of neurosurgical treatment and the quality of life of patients with drug resistant epilepsy and to determine what are the potential predictors of quality of life of patients with drug resistant epilepsy one year after neurosurgical treatment. SUBJECTS AND METHODS: The research was performed at the Referral Centre for Epilepsy, Department of Neurology, University Hospital Centre Zagreb from February 2015 to February 2020 with Ethics commitee approval. The study included 96 patients with drug resistant epilepsy who were examined for the quality of life before and one year after neurosurgical treatment using the form questionnaire "Quality of life in epilepsy" (QOILE-31) validated Croatian 1.0 version and the questionnaire to assess the degree of depression "Beck Depression Inventory I" (BDI-I) validated Croatian version. RESULTS: Of 96 patients with drug resistant epilepsy one year after neurosurgical treatment 46 (47.9%) patients remained completely free from epileptis seizures. Wilcoxon equivalent pair test showed that the number of epileptic seizures one year after neurosurgical treatment was significantly lower (median before neurosurgical treatment is 10; and after neurosurgical treatment is 1, p<0.001). The most informative potential statistically significant predictor variables of quality of life based on the criterion variables QOLIE-31 and BDI-I are: total disease duration in years (p=0.034), patient age (p=0.042), number of antiepileptics one year after neurosurgical treatment (p=0.001), the number of epileptic seizures per month (p=0.016), and social welfare rights (p=0.045). CONCLUSION: Neurosurgical treatment of patients with drug resistant epilepsy significantly reduces the number of epileptic seizures which significantly improves their overall quality of life one year after neurosurgical treatment.

QUALITY OF LIFE IN PATIENTS WITH EPILEPSY - SINGLE CENTRE EXPERIENCE.

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).

[CLINICAL GUIDELINES FOR DIAGNOSING, TREATING AND MONITORING OF ADULT PATIENTS WITH GLIOMAS OF CENTRAL NERVOUS SYSTEM]. / KLINICKE UPUTE ZA DIJAGNOZU, LIJECENJE I PRACENJE ODRASLIH BOLESNIKA OBOLJELIH OD GLIOMA SREDISNJEGA ZIVCANOG SUSTAVA.

Gliomas of the central nervous system are glial cell tumors that are divided in low and high grade group. Multidisciplinary approach to treatment consists of surgery, radiotherapy and chemotherapy. The type and order of treatment depend on the characteristics of the tumor and the patient. We present the clinical guidelines for diagnostic procedures, surgical treatment, oncological treatment and follow up of patients with this type of tumor in the Republic of Croatia.

Electroencephalographic Response to Different Odors in Healthy Individuals: A Promising Tool for Objective Assessment of Olfactory Disorders.

The aim of the present study was to examine human central nervous system response to three different odors. Electrophysiological activity was recorded in the baseline state and for 3 odors, lemon, peppermint, and vanilla, in 16 healthy participants. Electrodes were separated into groups according to the spatial position on the head. Fast Fourier transformation was performed on every set, and mean value of activity in theta was exported. As theta showed statistically significant results, further analysis was based only on the theta frequency band. On electrodes FP1, F3, Fz, F4, F8, T7, C3, Cz, C4, T8, TP9, CP5, CP1, CP2, CP6, P7, P3, Pz, P4, P8, PO9, and PO10 there was statistically significant difference in the electrical activity of the brain between four conditions. For peppermint and lemon, there was statistically significant difference in activity between different regions-F(1.576, 23.637)=16.030, P=.000 and F(1.362, 20.425)=4.54, P=.035, respectively-where the activity in the central area was significantly reduced compared with the activity in the other 4 areas and in the left and right anterior and left posterior area, respectively. There was no statistically significant difference for vanilla between specific areas, F(1.217, 18.257)=1.155, P=.309. The results indicate that olfactory stimuli can affect the frequency characteristics of the electrical activity of the brain.

Tongue somatosensory-evoked potentials in microvascular decompression treated trigeminal neuralgia.

Somatosensory-evoked potentials of the tongue (tSSEP) provide useful information about trigeminal-afferent pathway. The aim of this study was to evaluate tSSEP in trigeminal neuralgia (TN) treatment with microvascular decompression. Two patients with trigeminal neuralgia refractory to conservative treatment underwent microvascular decompression of the trigeminal nerve. tSSEP was performed a month prior to surgery and in the month after the surgery in both patients. Pain frequency and tSSEP were analyzed before and after surgery. In both patients, a complete resolution of pain occurred. In patient 1, tSSEP latencies became shorter than before surgery and wave N1 appeared. The intensity of stimulation necessary to reach the threshold was 4 mA before the surgery and 1 mA after the surgery. A complete recovery of tSSEP after the operation was achieved in patient 2. The results of present study demonstrate potential value of tSSEP in pre-surgery evaluation and post-surgery follow-up of TN patients.

Personalized medicine in neurodegenerative diseases: how far away?

Neurodegenerative diseases are characterized by progressive dysfunction of the nervous system as a result of neuronal loss in the brain and spinal cord. Despite extensive research efforts aimed at development of new disease-modifying therapeutics, there is still no effective treatment to halt neurodegenerative processes. Thus, modification of current therapeutic and diagnostic research strategies is a goal of increasing urgency. The biggest limitation in neurodegenerative disease research is the lack of appropriate biomarkers. Discovery of universal biomarkers capable of diagnosing patients with neurodegenerative diseases, monitoring their response to therapy, and predicting disease progression seems to be a tall order. Instead, a combination of different methodologies in the discovery of biomarkers specific for each described aspect of the disease seems to be a more viable approach. Although application of personalized medicine in diagnosis and treatment of neurodegenerative diseases may seem far off, some recent developments, such as utilizing specific biological therapies in multiple sclerosis, microRNA profiling as a source of novel biomarkers in Parkinson's disease, or combination of neuroimaging and proteomic analyses in diagnosis of Alzheimer's disease patients, already point to the way clinical neurology may integrate new achievements in everyday practice. Combination of genomic, proteomic, glycomic, and metabolomic approaches may yield novel insights into molecular mechanisms of disease pathophysiology, which could then be integrated and translated into clinical neurology. Based on the developments during the past decade, it is feasible to predict that a personalized approach to treating neurological disorders will become more widely applicable in the coming years.

Factors associated with perceived stigma of epilepsy in Croatia: a study using the revised Epilepsy Stigma Scale.

PURPOSE: It is believed that a large number of factors influence feelings of stigma, but their relative contribution is not yet entirely clear. Most studies to date were conducted using the Epilepsy Stigma Scale (ESS); only one used a revised version of the ESS (rESS). The following study aims to determine factors contributing to epilepsy stigma in outpatients with chronic epilepsy in Croatia, and to analyze some psychometric properties of the Croatian translation of the rESS. METHODS: Alongside standard testing for validity of the scale, a simulation model of the original ESS (smESS) was created. This model, which does not include a grading Likert 0-3 scale, was compared with the rESS. RESULTS: In total, 159 out of 298 subjects (53%) reported feeling stigmatised, with 136 (45%) mild to moderately and 23 (8%) highly. Internal consistency of the Croatian translation of the rESS was 0.887. Feelings of stigma were significantly associated with age ≤ 50 years, younger age of epilepsy onset, more than 50 seizures to date, generalized tonic-clonic seizures, and a shorter seizure-free period. Multiple stepwise regression showed number of seizures to date as a significant variable (Beta=0.246). By adapting data into the smESS significant associations with younger age and age of epilepsy onset were lost. Internal consistency of the smESS was 0.849. CONCLUSIONS: The Croatian translation of the rESS has been proved to be a suitable instrument for diagnosing epilepsy stigma. The results of our model point to the possibility that the rESS might be more sensitive than the original ESS.

Signal hyperintensities on brain magnetic resonance imaging in patients with primary Sjögren syndrome and frequent episodic tension-type headache: relation to platelet serotonin level and disease activity.

OBJECTIVE: To examine differences in number and size of signal hyperintensities (SH) on magnetic resonance imaging (MRI) between patients with primary Sjögren syndrome (pSS) and controls who all had frequent episodic tension-type headache (FETH), and to investigate their relation to platelet serotonin level (PSL), patient age, disease duration, and activity. METHODS: SH in 22 pSS patients with FETH were compared to 20 aged-matched controls with FETH, using the modified semiquantitative rating scale. Spectrofluorimetry was used for determination of PSL, and the European League Against Rheumatism SS Disease Activity Index (ESSDAI) for disease activity assessment. RESULTS: Statistically significant differences in the total number of SH were noted infratentorially (p = 0.025) and in the basal ganglia for lesions of diameter > 5 mm (p = 0.048). Significant correlations were found between disease duration and number of overall lesions > 5 mm (p = 0.04) and subcortical lesions of diameter 2-5 mm (p = 0.035). Number of periventricular SH inversely correlated to PSL (p = 0.019) and to patient age (p = 0.004), without association with markers of immunoinflammation and ESSDAI. CONCLUSION: Our study showed that SH on brain MRI are more common in specific regions of the brain in pSS patients with FETH than in controls with FETH, signifying a more widespread cerebral vasculopathy in SS patients with FETH. Periventricular SH seem to be associated to increased platelet serotonin release in pSS patients with FETH and correlated with disease duration, without correlation to the actual ESSDAI and markers of immunoinflammation, and might be linked with chronic immunoinflammation of low-grade intensity and vasculitis in pSS.

Clinical and neurophysiological changes in patients with pineal region expansions.

In the last 20 years neurological and neurosurgical follow up of our patients with pineal region expansions (118 patients) pointed to certain clinical and neurophysiological regularities. We performed retrospective study which included 84 patients with pineal region expansions in the period from 1992 to 2009. The study included 55 women and 29 men, mean age 30.08 +/- 13.93 years, with positive brain magnetic resonance imaging (MRI)--70 patients (83.4%) had simple pineal gland cysts, and 14 patients (16.67%) had expansive process in pineal region with compressive effect. All patients had headache, while 32 patients (38%) had epileptic phenomena--primary generalized seizures. Patients had common electroencephalography (EEG) pattern with paroxysmal discharges of 3Hz (or more than 3 Hz) spike-and-wave complexes. Operation with supracerebellar infratentorial approach was performed in 70 patients. In most of our patients indication for the operation was established based on the size of the cyst (15 mm or more), with the signs of compression on the quadrigeminal plate and compression of the surrounding veins, which could result in seizures and EEG changes verified in our group of patients. Pathohistological analysis revealed pineocytomas in 11 cases (15.71%), pinealoblastomas in 2 cases (2.86%), one case of teratoma (1.43%), while 56 patients had pineal gland cysts (80%). Following surgery clinical condition improved in all patients--patients became seizure-free and headaches significantly decreased. Other symptoms including diplopiae, nausea, vomiting, vertigo as well as blurred vision also disappeared. There were no complications after surgical procedures. This study points to often appearance of seizures that clinically and neurophysiologically present as primary generalized epilepsy in patients with pineal region expansions. Our hypotheses are that mass effect on the surrounding veins that affects normal perfusion, compressive effect on the quadrigeminal plate and the aqueduct of the midbrain, hemosiderin deposists, as well as secretion disturbances of anticonvulsive agent melatonin can be involved in the pathogenesis of seizures. We suggest to perform high resolution brain MRI with special demonstration of pineal region in all young patients that have seizures and specific EEG changes.

Short pain-provoked head-up tilt test for the confirmation of vasovagal syncope.

We investigated a short pain-provoked head-up tilt (PP-HUT) and the Calgary Syncope Symptom Score in a group of patients with clinically diagnosed vasovagal syncope and group of neurological patients without transient loss of consciousness. We included 127 consecutive patients who were investigated in our laboratory. The group 1 included 56 patients who after appropriate investigations were diagnosed with vasovagal syncope. The group 2 included 70 neurological patients without transient loss of consciousness. The subjects were tilted to 70° for a maximum period of 10 min or until symptoms occurred. If there were no symptoms after initial 10 min, a painful stimulus with the insertion of 0.7 mm needle into the dorsum of hand subcutaneously for 30 s was performed with the patient in the tilted for further 5 min. Calgary Syncope Symptom Score was calculated for all patients. In the group 1, significantly higher number of patients had positive results on PP-HUT (36 vs. 6 patients, respectively; p < 0,001). There was no difference in the presence of orthostatic hypotension (8 vs. 15 patients, respectively; p = 0.36) or postural orthostatic tachycardia syndrome (3 vs. 1 patient, respectively; p = 0.32) between groups. PP-HUT had sensitivity of 65.9 % (95 % CI 0.49-0.79) and specificity of 89.7 % (95 % CI 0.75-0.97). The CSSS had sensitivity of 58.5 % (95 % CI 0.42-0.73) and specificity of 46.1 % (95 % CI 0.30-0.63). PP-HUT has a higher diagnostic rate than the CSSS and provides a rapid alternative to conventional methods.

Vagus nerve stimulation in Lafora body disease.

INTRODUCTION: Lafora body disease (LBD) is a rare autosomal recessive disorder characterized by progression to inexorable dementia and frequent occipital seizures, in addition to myoclonus and generalized tonic-clonic seizures (GTCSs). It belongs to the group of progressive myoclonus epilepsies (PMEs), rare inherited neurodegenerative diseases with great clinical and genetic differences, as well as poor prognosis. Since those patients have a pharmacoresistant disease, an adjunctive treatment option is vagus nerve stimulation (VNS). To date, there are four reported cases of the utility of VNS in PME - in Unverricht-Lundborg disease (ULD), myoclonic epilepsy with ragged-red fibers (MERRF), Gaucher's disease, and in one case that remained unclassified. CASE PRESENTATION: A 19-year-old male patient had progressive myoclonus, GTCSs that often progressed to status epilepticus (SE), progressive cerebellar and extrapyramidal symptomatology, and dementia, and his disease was pharmacoresistant. We confirmed the diagnosis of LBD by genetic testing. After VNS implantation, in the one-year follow-up period, there was a complete reduction of GTCS and SE, significant regression of myoclonus, and moderate regression of cerebellar symptomatology. CONCLUSION: To our knowledge, this is the first reported case of the utility of VNS in LBD. Vagus nerve stimulation therapy may be considered a treatment option for different clinical entities of PME. Further studies with a larger number of patients are needed.

Association between lamotrigine concentrations and ABCB1 polymorphisms in patients with epilepsy.

BACKGROUND: Epilepsy is treated with a variety of anticonvulsants that are often used concomitantly. Therefore, therapeutic drug monitoring is often necessary. Along with clinical and environmental factors, genetic predisposition has been recognized to be relevant for interindividual variability in drug response. Polymorphic transporter proteins such as P-glycoprotein significantly influence pharmacokinetics and bioavailability of many structurally unrelated drugs. The aim of the study was to evaluate the impact of polymorphisms in the P-glycoprotein-encoding gene ABCB1 (C1236T, G2677T/A, C3435T) on antiepileptic drug disposition. METHODS: We recruited 222 patients with epilepsy who were prescribed lamotrigine in monotherapy or polytherapy. Lamotrigine plasma concentrations were analyzed and compared with ABCB1 gene variants. The ABCB1 genotyping was performed by real-time polymerase chain reaction methods. The therapeutic drug monitoring was performed by high-performance liquid chromatography-diode array detector (DAD) and immunoassay. RESULTS: A significant correlation was confirmed between lamotrigine concentration and additional drugs (P < 0.001). In the whole group, statistical analysis showed correlations between lamotrigine concentrations and ABCB1 C1236T variants: 10.1 and 6.5 µmol/L for CC versus CT + TT, respectively (P = 0.021), and for dose corrected lamotrigine 0.068 and 0.053 µmol·L·mg, for CC versus CT + TT, respectively (P = 0.017). Analysis of a specific haplotype showed that 1236C-2677G-3435C carriers had higher lamotrigine concentrations than 1236T-2677G-3435T carriers (P < 0.001), followed by 1236T-2677T-3435C carriers (P < 0.001). CONCLUSIONS: ABCB1 C1236T, G2677T/A, C3435T polymorphisms have an influence on lamotrigine serum concentrations.

Recommendations for diagnosis and management of multiple sclerosis.

Multiple sclerosis (MS) is a chronic demyelinating neurologic disorder that mainly affects young individuals (aged 20 to 50 years). Approximately 85% of patients experience an initial course with relapses and remissions (relapsing-remitting multiple sclerosis). Guidelines for the management of MS should be focused on three main areas: (a) the diagnosis of MS; (b) treatment of relapses; and (c) long-term preventive treatment including clinical follow up, dose adjustment, drug switch, control of therapeutic efficacy, and disease progression. Diagnosis should be established according to clinical and paraclinical criteria. Discussion on therapeutic recommendations is focused on the disease-modifying agents in acute phases and drugs for long-term treatment and symptomatic treatment. Differential diagnoses must be taken into account on making the diagnosis of MS. Therefore, diagnosis of MS should be established on clinical and radiological diagnostic criteria, cerebrospinal fluid analysis and evoked potentials.