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Objective: Phenylketonuria (PKU) is the most common form of amino acid metabolism disorders with autosomal recessive inheritance. The brain damage can be prevented by early diagnosis and a phenylalanine-restricted diet. Untreated or late-treated patients may show mental retardation and other cognitive dysfunctions, as well as motor disability and/or epilepsy., Methods: Three patients with PKU and epilepsy were recognized to have reflex epileptic features, and there were ten consecutive adult patients with PKU and epilepsy who were evaluated retrospectively. Medical history, ages at diagnosis and therapy onset, age at seizure onset, seizure types and reflex features, neurological findings, cranial imaging, electroencephalography (EEG) findings, and final clinical condition were evaluated. Reflex epilepsy features were examined in detail., Results: The cases (6 females, 4 males) were diagnosed at ages between 3.5months and 12years. All patients had various degrees of mental-motor retardation and focal or generalized seizures with age at seizure onset varied between neonatal period and 15years. Three patients had febrile seizure, 3 patients had myoclonia, and 3 patients had status epilepticus. All patients had abnormal EEG findings except one. There was a slowing of background activity, and generalized discharges were observed in 7 patients; 3 of them had asymmetrical discharges. One patient had right hippocampal sclerosis (HS), and another patient had hypointensities in the basal ganglia and corpus callosum. Reflex features were clinically observed in 3 of the patients; however, EEG results did not show any related findings. One patient had reflex seizures triggered by photic stimuli, hot water, and startling; one by photic stimuli; and the other one by startling., Conclusion: Reports on the clinical and electrophysiological features of adult patients with PKU were scant. We emphasized that reflex clinical features may be observed in this metabolic disease, and focal epileptiform abnormalities and asymmetry may be present in electrophysiological evaluation besides the rare association with HS., (Copyright © 2018 Elsevier Inc. All rights reserved.)

High-frequency oscillations in local field potentials recorded with intracranial EEG are putative biomarkers of seizure onset zones in epileptic brain. However, localized 80-500 Hz oscillations can also be recorded from normal and non-epileptic cerebral structures. When defined only by rate or frequency, physiological high-frequency oscillations are indistinguishable from pathological ones, which limit their application in epilepsy presurgical planning. We hypothesized that pathological high-frequency oscillations occur in a repetitive fashion with a similar waveform morphology that specifically indicates seizure onset zones. We investigated the waveform patterns of automatically detected high-frequency oscillations in 13 epilepsy patients and five control subjects, with an average of 73 subdural and intracerebral electrodes recorded per patient. The repetitive oscillatory waveforms were identified by using a pipeline of unsupervised machine learning techniques and were then correlated with independently clinician-defined seizure onset zones. Consistently in all patients, the stereotypical high-frequency oscillations with the highest degree of waveform similarity were localized within the seizure onset zones only, whereas the channels generating high-frequency oscillations embedded in random waveforms were found in the functional regions independent from the epileptogenic locations. The repetitive waveform pattern was more evident in fast ripples compared to ripples, suggesting a potential association between waveform repetition and the underlying pathological network. Our findings provided a new tool for the interpretation of pathological high-frequency oscillations that can be efficiently applied to distinguish seizure onset zones from functionally important sites, which is a critical step towards the translation of these signature events into valid clinical biomarkers.awx374media15721572971001.

Functional mapping of eloquent cortex before the resection of a tumor is a critical procedure for optimizing survival and quality of life. In order to locate the hand area of the motor cortex in two patients with low-grade gliomas (LGG), we recorded electrocorticogram (ECoG) from a 113 channel hybrid high-density grid (64 large contacts with diameter of 2.7 mm and 49 small contacts with diameter of 1 mm) while they executed hand clenching movements. We investigated the spatio-spectral characteristics of the neural oscillatory activity and observed that, in both patients, the hand movements were consistently associated with a wide spread power decrease in the low frequency band (LFB: 8-32 Hz) and a more localized power increase in the high frequency band (HFB: 60-280 Hz) within the sensorimotor region. Importantly, we observed significant power increase in the ultra-high frequency band (UFB: 300-800 Hz) during hand movements of both patients within a restricted cortical region close to the central sulcus, and the motor cortical "hand knob." Among all frequency bands we studied, the UFB modulations were closest to the central sulcus and direct cortical stimulation (DCS) positive site. Both HFB and UFB modulations exhibited different timing characteristics at different locations. Power increase in HFB and UFB starting before movement onset was observed mostly at the anterior part of the activated cortical region. In addition, the spatial patterns in HFB and UFB indicated a probable postcentral shift of the hand motor function in one of the patients. We also compared the task related subband modulations captured by the small and large contacts in our hybrid grid. We did not find any significant difference in terms of band power changes. This study shows initial evidence that event-driven neural oscillatory activity recorded from ECoG can reach up to 800 Hz. The spatial distribution of UFB oscillations was found to be more focalized and closer to the central sulcus compared to LFB and HFB. More studies are needed to characterize further the functional significance of UFB relative to LFB and HFB.

Purpose: We aimed to determine the location and vertical distance of the umbilicus relative to the aortic bifurcation using computed tomography (CT), and assess their relationship with BMI among Turkish women and their implications for laparoscopic entry., Methods: This cross-sectional study included a total of 209 women undergoing abdominopelvic CT; the vertical distance between the aortic bifurcation and the umbilicus was evaluated on coronal sections. The distance between the skin and the parietal peritoneum was measured from the umbilical pit to the peritoneum, and the distance between the skin and the aorta was measured from the umbilical pit to the surface of the aortic bifurcation. The measurements were performed along the sagittal plane. The age, height, and weight of the patients were recorded. For comparison, women were divided into three groups according to BMI., Results: The aortic bifurcation was located above (cephalic to) the umbilicus in 30 patients in the non-obese group (48.4%), 54 patients in the overweight group (55.7%), and 34 patients (68%) in the obese group. The mean distances between the umbilicus and the parietal peritoneum were 15.1 ± 6.4, 19 ± 5.5, 27.2 ± 10.8 mm, respectively, in the non-obese group, overweight group, and obese group. The mean distances between the umbilicus and the aorta were 85.8 ± 26.3, 110 ± 2.9, 132.1 ± 26.7 mm, respectively, in the non-obese group, overweight group, and obese group., Conclusions: The location of the umbilicus relative to the aortic bifurcation can vary according to age, BMI and ethnicity or nationality of patients; therefore, a surgeon should not stick to a particular angle of insertion during laparoscopic entry. It is better for surgeons to know their unique patient population.

There have been recent reports of antibody-mediated status epilepticus. The objective of our study was to investigate the prevalence of neuronal autoantibodies in patients with status epilepticus (SE) with unresolved etiology. The presence of neuronal autoantibodies was investigated prospectively in adult patients with SE who presented to our clinic between February 2012 and December 2013 with unresolved etiology. Clinical and electrophysiologic features of seropositive patients were recorded. Also, seronegative and seropositive patient groups were compared in terms of demographic and clinical features, treatment responses, and outcomes. Neuronal antibodies against N-methyl-D-aspartate receptor (NMDA-R) were positive in 2 patients, against glycine receptor (Gly-R) in 2 patients, and against gamma-aminobutyric acid-A receptor [GABA(A)R] in 1 patient, which constituted a total of 5 (22.7%) of 22 patients with SE with unidentified etiology. One of three patients with systemic tumors was positive for GABA(A)R antibody. Four patients had a short epilepsy duration, while one of the NMDA-R antibody-positive patients had chronic epilepsy and double cortex finding in MRI. There was no significant difference between seropositive and seronegative patient groups in terms of demographic and clinical features, treatment responses, and outcomes. Neuronal antibodies are found in a sizeable portion of de novo SE patients, who are potential candidates of autoimmune encephalitis. Alternatively, these antibodies may presumably also emerge in SE patients with a chronic epilepsy history as an epiphenomenon. Further research is required to make the distinction between these two different antibody formation mechanisms.

Purpose: There is a lack of knowledge on consecutive patients with epilepsy associated with bilateral hippocampal sclerosis (BHS). We aimed to investigate the differentiating features of BHS in comparison with unilateral HS (UHS)., Method: We investigated our database for patients with epilepsy fulfilling the major magnetic resonance imaging criteria for BHS; namely, presence of bilateral atrophy and high signal changes on T2 and FLAIR series in the hippocampi. UHS patients seen in past 2 years were included as the control group. Clinical, EEG, and other laboratory findings, data on treatment response and epilepsy surgery were investigated from their files., Results: A total of 124 patients (31 with BHS and 93 with UHS; 49 right-sided and 44 left-sided) were included. We found that 16.1% of the BHS and 18.3% of the UHS groups were not drug-refractory. A binary logistic regression analysis performed with significant clinical features disclosed that history of febrile status epilepticus, mental retardation, and status epilepticus were statistically more common in BHS group. Moreover, diagnosis of psychosis established by an experienced psychiatrist and slowing of the EEG background activity were both found significantly more frequent in BHS. 66.67% of the operated BHS patients showed benefit from epilepsy surgery., Conclusions: BHS is a heterogeneous group, showing significant differences such as increased frequencies of mental retardation, status epilepticus, febrile status epilepticus and psychosis, in comparison to UHS. In all, 16.1% of the BHS cases showed a benign course similar to the UHS group and some patients with drug-resistant epilepsy may show benefit from epilepsy surgery.

Purpose: We aimed to investigate juvenile myoclonic epilepsy (JME) patients complaining of tremor unrelated to valproate (VPA) treatment and evaluate if there were differences between JME patients with and without tremor and essential tremor (ET) patients to exclude comorbidity., Methods: Fifteen JME cases with the complaint of tremor, 14 JME patients without tremor, 14 patients with ET and 14 healthy subjects (HS) were included. Regularity, frequency and amplitude of the tremor and superimposed myoclonia were assessed by accelerometric analysis. Cortical SEPs evoked by the stimulation of the median nerve were recorded bilaterally. Clinical and neurophysiologic features were statistically compared between the groups., Findings: Amplitude of postural tremor of the left hand was significantly increased in the ET group compared to JME patients with tremor, but there were no differences regarding to frequency. Strikingly, there were superimposed irregular, low-amplitude inconstant myoclonic jerks located to distal part of the fingers in JME group with tremor. Initial frequency of myoclonic seizures was also significantly higher in this group compared to JME patients without tremor but this difference disappeared after treatment. The group of JME with tremor had the highest N20-P25 and P25-N35 amplitudes, followed by JME without tremor, ET and HS, respectively., Conclusion: Tremulous hand movements in JME resembled ET, but their amplitude was lower and characterized with accompanying irregular myoclonic jerks. The presence of tremor in JME patients should be taken into consideration to create more homogeneous groups in genetic and pathophysiological studies of JME., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objectives: Transcranial direct current stimulation (tDCS) is a non-invasive and safe method tried in drug-resistant epilepsies, in recent years. Our aim was to evaluate the effect of tDCS in patients diagnosed with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) which is a well-known drug-resistant focal epilepsy syndrome., Patients and Methods: Twelve MTLE-HS patients diagnosed with their typical clinical, EEG and MRI findings fulfilling the criteria for drug-resistance as suggested by the ILAE commission were included after Ethics Committee approval and their signed consent. All patients received modulated cathodal stimulation; 2mA for 30min on 3 consecutive days. All patients also received sham stimulation with the same electrode positions; designed as 60s stimulation gradually decreasing in 15s with placement of the electrodes for 30min over the stimulation side. They were followed up by standard seizure diaries and their medical treatment was not changed during the study period. Their seizure frequencies both before and after cathodal tDCS and sham stimulation were compared statistically. Adverse effects were also questioned., Results: Mean age of our study group was 35.42±6.96 (6 males; median: 35.50). The mean seizure frequency was 10.58±9.91 (median=8; min-max=2-30) at the baseline and significantly decreased to 1.67±2.50 (median=0.5; min-max=0-8) after cathodal tDCS application (p=0.003). Ten patients (83.33%) had more than 50% decrease in their seizure frequencies after cathodal tDCS. Two patients (16.67%) also showed positive sham effect. Six patients (50%) were seizure-free in the post-cathodal tDCS period of one month. No adverse effect has been reported except tingling sensation during cathodal stimulation., Conclusion: Our small series suggested that cathodal tDCS may be used as an additional treatment option in MTLE-HS. It may be tried in TLE-HS patients waiting for or rejecting epilepsy surgery or even with ineffective surgery results. More studies are needed with large series of patients to investigate the effects of tDCS in drug resistant epilepsies., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: The attitude of patients with epilepsy towards their disease is an important factor in disease management and quality of life. The aim of this study was to define the attitudes of patients with epilepsy towards their disease and the factors that affect their attitudes., Patients and Method: This descriptive study was performed on patients admitted to an epilepsy outpatient clinic of a university hospital between May and September 2015. The sample consisted of 70 patients over 18years of age with a diagnosis of epilepsy and no health problem other than epilepsy. Patients with no seizure in the last two years were excluded. The Epilepsy Attitude Scale was used to evaluate attitudes of the patients towards epilepsy; the Epilepsy Knowledge Scale, Rotter's Locus of Control Scale, Hospital Anxiety and Depression Scale (HADS), and the Quality of Life in Epilepsy-10 (QOLIE-10) were used to investigate the attitude-related factors., Results: Among the 70 participants, 43 were female, and the mean age was 31.4years. The educational level of the patients was lower (primary school) in 38.6% of the sample, and 18.6% were unemployed. Time since diagnosis was 15.1years, 75.7% of the participants had generalized type of seizures, and more than half had seizures more frequently than once a month. The mean score of the attitude scale was 59.7±6.62 (range: 14-70). The attitudes of the patients towards epilepsy were found to be related to their educational status, living alone, and the attitudes of their families. The attitude scores were also related to the level of knowledge on epilepsy, stigma, and depression. Furthermore, the attitude was found to be correlated with quality of life., Conclusion: Patients with epilepsy had moderate-to-good attitude towards their disease. It was observed that the attitude was related to the knowledge, stigma, and depression rather than to demographic factors and the seizures, and furthermore, the attitude was found to be correlated with quality of life., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Our aim was to investigate the prevalence of neuronal autoantibodies (NAbs) in a large consecutive series with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) and to elucidate the clinical and laboratory clues for detection of NAbs in this prototype of frequent, drug-resistant epilepsy syndrome., Methods: Consecutive patients diagnosed with MTLE fulfilling the MRI criteria for HS were enrolled. The sera of patients and various control groups (80 subjects) were tested for eight NAbs after ethical approval and signed consents. Brain tissues obtained from surgical specimens were also investigated by immunohistochemical analysis for the presence of inflammatory infiltrates. The features of seropositive versus seronegative groups were compared and binary logistic regression analysis was performed to explore the differentiating variables., Results: We found antibodies against antigens, contactin-associated protein-like 2 in 11 patients, uncharacterised voltage-gated potassium channel (VGKC)-complex antigens in four patients, glycine receptor (GLY-R) in 5 patients, N-methyl-d-aspartate receptor in 4 patients and γ-aminobutyric acid receptor A in 1 patient of 111 patients with MTLE-HS and none of the control subjects. The history of status epilepticus, diagnosis of psychosis and positron emission tomography or single-photon emission CT findings in temporal plus extratemporal regions were found significantly more frequently in the seropositive group. Binary logistic regression analysis disclosed that status epilepticus, psychosis and cognitive dysfunction were statistically significant variables to differentiate between the VGKC-complex subgroup versus seronegative group., Conclusions: This first systematic screening study of various NAbs showed 22.5% seropositivity belonging mostly to VGKC-complex antibodies in a large consecutive series of patients with MTLE-HS. Our results indicated a VGKC-complex autoimmunity-related subgroup in the syndrome of MTLE-HS., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: High frequency oscillations (HFOs) in intracranial electroencephalography (iEEG) recordings are considered as promising clinical biomarkers of epileptogenic regions in the brain. The aim of this study is to improve and automatize the detection of HFOs by exploring the time-frequency content of iEEG and to investigate the seizure onset zone (SOZ) detection accuracy during the sleep, awake and pre-ictal states in patients with epilepsy, for the purpose of assisting the localization of SOZ in clinical practice., Approach: Ten-minute iEEG segments were defined during different states in eight patients with refractory epilepsy. A three-stage algorithm was implemented to detect HFOs in these segments. First, an amplitude based initial detection threshold was used to generate a large pool of HFO candidates. Then distinguishing features were extracted from the time and time-frequency domain of the raw iEEG and used with a Gaussian mixture model clustering to isolate HFO events from other activities. The spatial distribution of HFO clusters was correlated with the seizure onset channels identified by neurologists in seven patient with good surgical outcome., Main Results: The overlapping rates of localized channels and seizure onset locations were high in all states. The best result was obtained using the iEEG data during sleep, achieving a sensitivity of 81%, and a specificity of 96%. The channels with maximum number of HFOs identified epileptogenic areas where the seizures occurred more frequently., Significance: The current study was conducted using iEEG data collected in realistic clinical conditions without channel pre-exclusion. HFOs were investigated with novel features extracted from the entire frequency band, and were correlated with SOZ in different states. The results indicate that automatic HFO detection with unsupervised clustering methods exploring the time-frequency content of raw iEEG can be efficiently used to identify the epileptogenic zone with an accurate and efficient manner.

Autonomic dysfunction has frequently been reported in autoimmune encephalitis associated with seizures and there is growing evidence that epilepsy patients may display neuronal autoantibodies (NAAb). The aim of this study was to investigate the frequency of NAAb in epilepsy patients with peri-ictal autonomic findings. Fifty-eight patients (37 women/21 men; average age of 34.2 ± 9.9 years and epilepsy duration of 19.1 ± 9.6 years) who had at least one video-EEG recorded focal or secondary generalized seizure with clear-cut documented peri-ictal autonomic findings, or consistently reported seizures with autonomic semiology, were included. NAAb were tested by RIA or cell based assays. NAAb were present in 17 of 58 (29.3%) patients. Among seropositive patients, antibodies were directed against N-methyl-D-aspartate receptor (NMDAR) in 5 (29%), contactin-associated protein-like 2 (CASPR2) in 5 (29%), uncharacterized voltage gated potassium channel (VGKC)-complex antigens in 3 (18%), glutamic acid decarboxylase (GAD) in 2 (12%), glycine receptor (GLYR) in one (6%) and type A gamma aminobutyric acid receptor (GABAAR) in one patient (6%). Peri-ictal gastrointestinal manifestations, piloerection, ictal fever, urinary urge, and cough occurred more commonly in the seropositive group. The prevalences of psychotic attacks and status epilepticus were significantly increased in the seropositive group. Seropositivity prevalence in our patient group with peri-ictal autonomic findings is higher than other previously reported epilepsy cohorts. In our study, ictal fever-VGKC-complex antibody and pilomotor seizure-GABAAR antibody associations were documented for the first time. Chronic epilepsy patients with peri-ictal autonomic semiology, history of status epilepticus and psychotic disorder may benefit from autoantibody screening.

Uterine arteriovenous malformation (AVM) is defined as abnormal and nonfunctional connections between the uterine arteries and veins. Although the patients typically present with vaginal bleeding, some patients may experience life-threatening massive bleeding in some circumstances. The treatment of choice depends on the symptoms, age, desire for future fertility, and localization and size of the lesion; however, embolization of the uterine artery is the first choice in symptomatic AVM in patients at reproductive age with expectations of future fertility. We report a case of acquired AVM (after D/C) with an extensive lesion, which was successfully treated with bilateral uterine artery embolization (UAE).

Objective: To assess the efficacy of intravenous (IV) levetiracetam (LEV) in the treatment of status epilepticus (SE) and treatment outcomes., Methods: This study was conducted on patients, who were classified according to the clinical characteristics of their seizures, in the emergency department, neurology, and other services of our hospital. Patients were administrated IV LEV for the treatment of their SE after failing to respond to IV diazepam., Results: We prospectively investigated 30 patients, 16 females and 14 males whose ages ranged between 17 and 90 years (55.6 ± 19.6). Fourteen patients had convulsive SE (CSE), 11 had nonconvulsive SE (NCSE), and 5 had epilepsia partialis continua (EPC). The patients were given IV LEV with dosages ranging between 1000 and 4000 mg/day. Twenty-nine of the patients continued to receive LEV orally as maintenance treatment. The most common etiologies were cerebrovascular diseases (n = 7) and brain tumors (n = 6). SE was terminated in 23 (76.6%) patients. In the 12 months that followed SE, 9 of our patients (30%) died and 4 patients could not be contacted. Fifteen patients reported having no adverse effects, whereas three had mild adverse effects. No major adverse effects or complications causing disability were observed in twelve patients who were unconscious., Conclusion: Treatment with IV LEV is well-tolerated and effective both in focal and generalized SE. IV LEV has the combined advantage of efficacy, safety, and ease of use, which qualifies it to be the first choice after benzodiazepines (BZD) in the treatment of SE. This is the first prospective study of IV LEV treatment in status epilepticus and has the longest follow-up period, one year., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Subacute sclerosing panencephalitis (SSPE) is caused by a persistent measles virus infection. Regulatory mechanisms can be responsible for a failure of immunosurveillance in children with SSPE. In this study, peripheral blood cells of 71 patients with SSPE and 57 children with other diseases were compared phenotypically. The proportions of CD4(+), CD8(+) T, and NK cells were homogenous, whereas total CD3(+) T and Treg (CD4(+)CD25(+)CD152(+)) cells were decreased in patients with SSPE. The proportion of CD8(+) T cells expressing the inhibitory NKG2A(+) receptor was also decreased (1.7% ± 1.7% vs. 2.6% ± 1.9%, p = 0.007) in patients with SSPE, whereas the proportion of NK cells expressing activating NKG2C was increased compared with the control group (30.0% ± 17.3% vs. 22.2% ± 17.0%, p = 0.039). The decrease in the number of cells with regulatory phenotype, the lower presence of the inhibitory NK receptors on CD8(+) cells, and higher activating NK receptors on NK cells in SSPE indicate an upregulation of these cell types that favors their response. This state of active immune response may be caused by chronic stimulation of viral antigens leading to altered regulatory pathways.

Background:  Subacute sclerosing panencephalitis (SSPE) is a late complication of measles infection. Immune dysfunction related to genetic susceptibility has been considered in disease pathogenesis. A functional single nucleotide polymorphism (SNP) of granzyme B gene (GZMB) reported in several pathologies may also be involved in susceptibility to SSPE., Patients and Methods:  An SNP (rs8192917, G → A, R→Q) was screened in 118 SSPE patients and 221 healthy controls (HC) by polymerase chain reaction-restriction fragment length polymorphism. Frequencies were compared between groups. In vitro production of GZMB was measured in controls with different genotypes., Results:  The SNP had a minor allele (G) frequency of 0.22 in patients and 0.31 in controls. GG genotype was significantly less frequent in patients (odds ratio, 0.23). G allele carriers produced relatively higher levels of GZMB, when stimulated in vitro., Conclusion:  These findings implicate possible effect of this genetic polymorphism in susceptibility to SSPE which needs to be confirmed in bigger populations., (Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: Mitochondria have an essential role in neuronal excitability and neuronal survival. In addition to energy production, mitochondria also play a crucial role in the maintenance of intracellular calcium homeostasis, generation of reactive oxygen species and mechanisms of cell death. There is a relative paucity of data about the role of mitochondria in epilepsy. Mitochondrial genome analysis is rarely carried out in the investigation of some diseases. In mesial temporal lobe epilepsies (MTLE) cases, genome analysis has never been used previously. The aim of this study is to show mitochondrial dysfunctions using genome analysis in patients with MTLE-hippocampal sclerosis (HS)., Methods: 44 patients with MTLE-HS and 86 matched healthy unrelated controls were included in this study. The patients were divided into four groups according to their clinical presentation as the following: Group 1 consists of patients with intractable epilepsy who refused operation; Group 2 of operated seizure free patients; Group 3 of operated patients with seizures; and Group 4 unoperated seizure free patients with or without antiepileptic drugs. Blood samples were used to isolate DNA. Parallel tagged sequencing was employed to allow pyrosequencing of 130 samples. Complete mtDNA is amplified in two overlapping fragments (11 and 9 kb). The PCR amplicons were pooled in equimolar ratios. Titanium kits were used to produce shotgun libraries according to the manufacturer's protocol., Results: The average coverage in total was 130 ± 30 and an average of 2365127 bases and 337 bp fragment length was received from all samples. The mean mtDNA heteroplasmy in patients was 26.35 ± 12.3 and in controls 25.03 ± 9.34. Three mutations had prominently high significance in patient samples. The most significantly associated variation was located in the MT-ATP-8 gene (8502 A>T, Asn46Ile) whereas the other two were in the MT-ND4 (11994 C>T, Thr412Ile) and MT-ND5 (13231 A>C, Lys299Gln) genes., Conclusions: We have observed that three mutations were significantly related to the presence of epilepsy. These mutations were found at the 8502, 11994, and 13,231 bp of mtDNA, which resulted in amino acid changes at the MT-ATP-8, MT-ND4 and MT-ND5 genes. Finding mutations can lead us to knowing more about the pathophysiology of the MTLE disease., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: Neuronal antibodies have been identified in patients with seizures as the main or sole symptom. Our aim was to investigate the prevalence of these autoantibodies in patients with focal epilepsy of unknown cause (FEoUC) and in the group having mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS)., Methods: We studied anti-neuronal antibodies of consecutive adult patients diagnosed with FEoUC and MTLE-HS in our epilepsy center. The clinical and laboratory features of antibody-positive patients were compared with those of seronegative patients. The responses to therapy have also been investigated., Results: Sera from 81 patients with epilepsy were tested. We found antibodies against glycine receptor (GLY-R) in 5 (6.2%), contactin-associated protein 2 (CASPR-2) in 4 (4.9%), N-methyl-d-aspartate receptor (NMDA-R) in 2 (2.5%), and voltage-gated potassium channel (VGKC)-complex in 2 (2.5%) of our patients with epilepsy. Psychotic attacks and nonspecific magnetic resonance imaging (MRI) white matter changes (WMCs) showed significant associations in seropositive patients (p = 0.003 and p = 0.03, respectively). Poor drug-response rates and total seizure counts were also higher in the seropositive patients but without reaching statistical significance. Three seropositive patients with previous epilepsy surgery showed typical histopathologic results for MTLE-HS, but not inflammatory changes. Moreover, some patients harboring these antibodies partly benefited from immunotherapy., Significance: We detected neuronal antibodies in one sixth of patients with focal epilepsy, GLY-R antibodies being the leading one. Psychosis or nonspecific MRI WMCs were frequent in the seropositive group. Our results suggested that relevant antibodies should be screened for a treatment possibility in these groups., (Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.)

Objectives: None of the classifications of psychogenic non-epileptic seizures (PNES) have been widely accepted and used by physicians so far. In this study we aimed at classifying PNES on the basis of a modified version of semiological seizure classification (SSC). We also sought to assess the interrater reliability (IRR) of the PNES diagnosis based on SSC., Methods: We classified PNES into four types on the basis of our modification of SSC: pseudoaura, dialeptic, motor, and special (atonic, astatic, hypotonic) spells. Pseudoauras were not included in the statistical analysis. Ninety-one PNES attacks were observed during the 55 video-EEG sessions recorded for all patients. The interrater agreement was assessed by the kappa coefficient., Results: Twenty-nine women (78·3%) and eight men (21·6%) were surveyed, with a mean age of 28·4 ± 9·6 (range 16-54). The final diagnosis of PNES was established after a mean of 4·5 ± 2·3 years following the onset of PNES attacks in the patients. The mean seizure duration in the PNES was 241 seconds and 40·5% of our patients had PNES longer than 300 seconds. Motor and special PNES were the most common types observed by all the raters. The kappa values for each pair were as follows: Observers I-II 0·51 (p = 0·000), Observers I-III 0·47 (p = 0·000), and Observers II-III 0·73 (p = 0·000)., Conclusions: Interobserver agreement was moderate and substantial for three observers who classified PNES according to our modified SSC. The modified version of SSC could be used without difficulty in classifying PNES. Using SSC for PNES both shortens the period before diagnosis and eliminates the need to learn another new and acceptable classification for PNES.

Introduction: Hippocampal sclerosis is the most common lesion in patients with mesial temporal lobe epilepsy. Recently, there has been growing evidence on the involvement of mitochondria also in sporadic forms of epilepsy. In addition, it has been increasingly argued that mitochondrial dysfunction has an important role in epileptogenesis and seizure generation in temporal lobe epilepsy. Although mtDNA polymorphisms have been identified as potential risk factors for neurological diseases, the link between homoplasmy and heteroplasmy within tissues is not clear. We investigated whether mitochondrial DNA (mtDNA) polymorphisms are involved in a case report of a patient with mesial temporal lobe epilepsy-hippocampal sclerosis (MTLE-HS)., Design: We report the whole genome mtDNA deep sequencing results and clinical features of a 36-year-old woman with MTLE-HS. We used pyrosequencing technology to sequence a whole mitochondrial genome isolated from six different regions of her brain and blood. To assess the possible role of mitochondrial DNA variations in affected tissues, we compared all specimens from different regions of the hippocampus and blood., Results: In total, 35 homoplasmic and 18 heteroplasmic variations have been detected in 6 different regions of the hippocampus and in blood samples. While the samples did not display any difference in homoplasmic variations, it has been shown that hippocampus regions contain more heteroplasmic variations than blood. The number of heteroplasmic variations was highest in the CA2 region of the brain and accumulated in ND2, ND4 and ND5 genes. Also, dentate and subiculum regions of the hippocampus had similar heteroplasmic variation profiles., Discussion: We present a new rare example of parallel mutation at 16223 position. Our case suggests that defects in mitochondrial function might be underlying the pathogenesis of seizures in temporal lobe epilepsy., (© 2013 Elsevier B.V. All rights reserved.)

Purpose: The purpose of this study was to analyze electrophysiological properties of four main stages of ictal patterns of patients with operated temporal lobe epilepsy related to hippocampal sclerosis., Methods: We included 48 patients with temporal lobe epilepsy-hippocampal sclerosis. Seizures were classified according to their electrophysiological properties and surgical outcomes as seizure-free and not seizure-free. The EEGs with artifacts at the beginning were analyzed separately., Results: The most frequent type of ictal onset patterns was rhythmic theta/alpha activity, which was correlated to seizure-free group, whereas "switch of lateralization" and "bitemporal asynchrony" correlated to not seizure-free group. When bilateral independent ictal propagation patterns emerged, seizures tended to predict the side of epileptogenic zone wrongly. As a later significant pattern, rhythmic theta/alpha activity lateralized the focus correctly. Seizure termination was significantly concordant with hippocampal sclerosis lateralization in the seizure-free group., Conclusion: Ictal onset pattern with rhythmic theta/alpha activity correlates well with seizure freedom. Morphology of later significant patterns was more important in determining the lateralization reliability than time of appearance. The EEGs with short artifacts at the beginning are seen to be valuable in presurgical evaluation. Lateralization of ictal termination ipsilateral to MRI indicates good prognosis after surgery. Scalp EEG monitoring helps predict epileptogenic zones and postsurgical outcomes.

An international workshop on juvenile myoclonic epilepsy (JME) was conducted in Avignon, France in May 2011. During that workshop, a group of 45 experts on JME, together with one of the founding fathers of the syndrome of JME ("Janz syndrome"), Prof. Dr. Dieter Janz from Berlin, reached a consensus on diagnostic criteria and management of JME. The international experts on JME proposed two sets of criteria, which will be helpful for both clinical and scientific purposes. Class I criteria encompass myoclonic jerks without loss of consciousness exclusively occurring on or after awakening and associated with typical generalized epileptiform EEG abnormalities, with an age of onset between 10 and 25. Class II criteria allow the inclusion of myoclonic jerks predominantly occurring after awakening, generalized epileptiform EEG abnormalities with or without concomitant myoclonic jerks, and a greater time window for age at onset (6-25years). For both sets of criteria, patients should have a clear history of myoclonic jerks predominantly occurring after awakening and an EEG with generalized epileptiform discharges supporting a diagnosis of idiopathic generalized epilepsy. Patients with JME require special management because their epilepsy starts in the vulnerable period of adolescence and, accordingly, they have lifestyle issues that typically increase the likelihood of seizures (sleep deprivation, exposure to stroboscopic flashes in discos, alcohol intake, etc.) with poor adherence to antiepileptic drugs (AEDs). Results of an inventory of the different clinical management strategies are given. This article is part of a supplemental special issue entitled Juvenile Myoclonic Epilepsy: What is it Really?, (Copyright © 2013 Elsevier Inc. All rights reserved.)

We present the characteristics of eating epilepsy (EE), which is an underrecognized and complex form of reflex epilepsy. The files of 8996 patients with epilepsy were investigated retrospectively and only 6 cases (0.067%) were found.  Four males and 2 females, aged 20 to 63 years, had focal seizures, mostly with dyscognitive and experiential aura triggered by eating, as well as spontaneous seizures. All had an initial precipitating event for seizures (such as head/birth trauma or encephalitis). In 4 patients, the seizures were induced in the middle of the meal or even closely after the end. In the remaining 2 cases the seizures were at the beginning of the meal, suggesting 2 different mechanisms. Two patients had normal magnetic resonance imaging (MRI), whereas the others had heterogeneous findings. The interictal electroencephalographs (EEGs) showed frequent spikes over a large area on the left temporal region in 5 and over the right temporal area in 1 case. We recorded eating-related seizures originating from the left temporal region in 3 cases. Positron-emission tomography (PET) investigations were concordant with the EEG foci in 2 patients. All but 1 had a therapy-resistant course. Our study suggested that EE is extremely rare and occurred many years after an initial precipitating event for seizures. These focal seizures, starting mostly with experiential/dyscognitive aura, usually originated from the left temporal region, had mostly a therapy-resistant course, and were triggered by different mechanisms during eating with a long latency in most of the cases.

Some patients with idiopathic/genetic generalized epilepsy (IGE) experience visual aura, which can confuse the diagnosis. We sought to determine the frequency and characteristics of visual auras in IGE patients. Among the 176 IGE patients, 4 men and 7 women reported visual auras (mean age - 24 years). Syndromic diagnoses were juvenile myoclonic epilepsy in four, eyelid myoclonia with absences (EMA) in three, juvenile absence epilepsy in three, and other in one. Visual auras consisted of flashing lights, macropsia, illusional movements, and blindness. Eyelid myoclonia with absences was significantly more common in the group with visual aura (3 of 11 patients vs. 8 of 165 IGE patients; P=0.02). Furthermore, photosensitivity was found significantly more common in IGE patients with visual aura (90% vs 46% of the total IGE patients) (P=0.004). In conclusion, the visual auras do not exclude a diagnosis of IGE. The presence of visual aura in the EMA syndrome is also remarkable., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Identifying psychiatric disorders rather than psychiatric symptoms might help to distinguish patients with psychogenic nonepileptic seizures (PNES) from those with epileptic seizures (ES). Patients with PNES (n=35), patients with ES (n=35), and healthy controls (n=37) were compared with respect to the prevalence of psychiatric disorders in this study. We tested the predictive power of having axis I psychiatric disorders, as well as personality disorders, in distinguishing ES from PNES. There was no significant difference between the patient groups in the prevalence of axis I psychiatric disorders. Personality disorders were more prevalent in the PNES group than in the ES group (P<0.05). Having a personality disorder was the only predictor for the PNES group. Having a personality disorder seems to be a more significant predictor for PNES than having an axis I psychiatric disorder. Greater attention should be paid to personality disorders in the differentiation of PNES and ES and the provision of effective treatment., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: The typical clinical presentation of subacute sclerosing panencephalitis (SSPE) includes behavioral and intellectual changes followed by myoclonia. However, there are a considerable number of SSPE cases which present with distinct clinical features that can lead to a diagnostic difficulty. In this report, we summarize the clinical features of patients with SSPE who have uncommon presentations or features of the disease or coexisting medical conditions which may lead to diagnostic difficulties., Methods: We studied 173 patients, all under the age of 17. Patients were included in the study group according to following criteria: onset of the disease before age 2 years, seizures occurring before the onset of myoclonia and/or behavioral symptoms, extrapyramidal or cerebellar signs and ocular manifestations as initial presenting symptoms, fulminant course including coma or death within 6 months. Additionally, patients with onset of SSPE at the setting of a known neurological disorder are defined as another group in the study., Results: Out of 173 patients with SSPE who were followed in two neurology centers, 31 (17.9%) met our criteria., Conclusions: We found a relative high frequency of these clinical features. Our findings suggest that clinicians should be aware of this clinical characteristics and rule out the disease in cases were other common causes have been excluded, especially in countries with insufficient measles immunization.

Aims: The mechanisms underlying the changes in blood-brain barrier (BBB) integrity and the generation of seizures in childhood associated with preexisting brain lesions like cortical dysplasia (CD) are poorly understood. We investigated the effects of levetiracetam (LEV) on BBB integrity and the survival during hyperthermic seizures in rats with CD., Main Methods: Pregnant rats were exposed to 145 cGy of gamma-irradiation on embryonic day 17. On postnatal day 28, hyperthermia-induced seizures were evoked in offspring with CD. To show the functional and morphological alterations in BBB integrity, quantitative analysis of sodium fluorescein (NaFlu) extravasation, immunohistochemistry and electron microscopy were performed., Key Findings: Seizure scores and mortality rates were decreased by LEV during hyperthermia-induced seizures in rats with CD (P<0.01). Increased NaFlu extravasation into brain by hyperthermia-induced seizures in animals with CD was decreased by LEV (P<0.01). While glial fibrillary acidic protein (GFAP) immunoreactivity slightly increased in brain sections of animals with CD during hyperthermia-induced seizures, LEV led to GFAP immunoreactivity comparable to that of controls. Decreased occludin immunoreactivity and expression in CD plus hyperthermia-induced seizures was increased by LEV. Opening of tight junctions and abundance of pinocytotic vesicles representing ultrastructural evidences of BBB impairment and severe perivascular edema were observed in animals with CD exposed to hyperthermia-induced seizures and LEV treatment led to the attenuation of these findings., Significance: These results indicate that LEV may present a novel approach for the protection of the BBB besides its antiepileptic impact on hyperthermic seizures in the setting of CD., (Copyright © 2010 Elsevier Inc. All rights reserved.)

This study investigates the effects of levetiracetam (LEV) on the functional and structural properties of blood-brain barrier (BBB) in pentylenetetrazole (PTZ)-kindled rats with cortical dysplasia (CD). Pregnant rats were exposed to 145 cGy of gamma-irradiation on embryonic day 17. In offsprings, kindling was induced by giving subconvulsive doses of PTZ three times per week for 45 days. While all kindled rats with CD died during epileptic seizures evoked by the administration of a convulsive dose of PTZ in 15 to 25 min, one week LEV (80 mg/kg) pretreatment decreased the mortality to 38% in the same setting. LEV caused a remarkable decrease (p<0.01) in extravasation of sodium fluorescein dye into the brain tissue of kindled animals with CD treated with convulsive dose of PTZ. Occludin immunoreactivity and expression remained essentially unchanged in all groups. Immunoreactivity for glial fibrillary acidic protein (GFAP) was observed to be slightly increased by acute convulsive challenge in kindled rats with CD while LEV pretreatment led to GFAP immunoreactivity comparable to that of controls. An increased c-fos immunoreactivity in kindled rats with CD exposed to convulsive PTZ challenge was also observed with LEV pretreatment. Tight junctions were ultrastructurally intact, whereas LEV decreased the increased pinocytotic activity in brain endothelium of kindled rats with CD treated with convulsive dose of PTZ. The present study showed that LEV decreased the increased BBB permeability considerably by diminishing vesicular transport in epileptic seizures induced by convulsive PTZ challenge in kindled animals with CD.

We report a patient with adolescent-onset, Rasmussen's encephalitis, presenting with intractable focal seizures, mild hemiparesis, cognitive impairment, dystonia, and severe hemiballism. His father had Behcet's disease, considered to be an autoimmune disorder. Recent reports have directly implicated the role of cytotoxic T lymphocytes in the pathogenesis of both Rasmussen's encephalitis and Behcet's disease. The occurrence of Behcet's disease and Rasmussen's encephalitis in the same family suggests involvement of common genetic factors such as HLA haplotypes in both autoimmune disorders. It is possible that members of this family are genetically susceptible to developing autoimmune conditions that have been precipitated by separate environmental triggers.

Cortical dysplasia (CD) is one of the major causes contributing to epileptogenesis associated with blood-brain-barrier (BBB) disturbances. The current study investigated the functional and ultrastructural changes of BBB in pentylenetetrazole (PTZ)-kindled rats with CD. Pregnant rats on E17 were exposed to 145 cGy of gamma-irradiation and offspring were used for experiments. The rats were given PTZ three times per week to induce kindling. The permeability of BBB was determined by using sodium fluorescein (NaFlu). Immunohistochemistry for occludin, GFAP and c-fos, western-blot analysis for occludin and electron microscopy for the ultrastructural alterations in BBB were performed. The brain level of NaFlu did not increase in rats with CD and/or kindling. Following administration of a convulsive dose of PTZ, a significant increase in BBB permeability was observed in kindled rats with CD. Occludin immunoreactivity and expression remained essentially unchanged in all groups. Slightly enhanced immunoreactivity for GFAP was observed in all groups except control. c-fos immunoreactivity in brain sections of kindled rats with CD displayed a striking increase by convulsive PTZ challenge. Tight junctions were ultrastructurally intact, whereas markedly increased number of pinocytotic vesicles was noted in brain endothelium of kindled rats with CD by convulsive dose of PTZ. The present study showed that epileptic seizures induced by convulsive PTZ challenge during kindling-mediated epileptogenesis in the presence of CD changed both functional and ultrastructural properties of the BBB and considerably enhanced transendothelial vesicular transport, while paracellular pathway was apparently not involved in this setting.

Objective: Cerebral cavernous malformations (CCM) are vascular malformations causing seizures and cerebral hemorrhages. They occur in sporadic and familial forms. Familial cases are associated with a high frequency of multiple lesions, which are less frequently associated with sporadic cases., Case Report: We report a 46-year-old woman presenting with epilepsy with multiple cerebral cavernomatosis on MRI. Because she had had a previous liver transplantation operation, and received immunosuppressants, she was not advised to have a brain operation. However, she had to be operated as a result of a bleeding in one of her cerebral cavernomas. The histologic diagnosis was cavernoma. She has been seizure free after the operation with levetiracetam therapy for the last 17 months. She had no positive family history for both epilepsy and cavernomatosis., Conclusion: When multiple cerebral cavernomatosis are identified in a patient, a detailed neurologic family history should be sought despite the possibility of its being a sporadic case. Our main intention is to present a patient who is surgically controversial and to point out the importance of genetic heredity.

We investigated the effects of lipopolysachharide (LPS) on functional and structural properties of the blood-brain barrier (BBB) during pentylenetetrazole (PTZ)-induced epileptic seizures in rats. Arterial blood pressure was significantly elevated during epileptic seizures irrespective of LPS pretreatment. Plasma levels of interleukin (IL)-1, interleukin (IL)-6, nitric oxide (NO) and malondialdehyde (MDA) increased while catalase concentrations decreased in animals treated with LPS, PTZ and LPS plus PTZ. The significantly increased BBB permeability to Evans blue (EB) dye in the cerebral cortex, diencephalon and cerebellum regions of rats by PTZ-induced seizures was markedly reduced upon LPS pretreatment. Immunoreactivity for tight junction proteins, zonula occludens-1 and occludin, did not change in brain vessels of animals treated with PTZ and LPS plus PTZ. Glial fibrillary acidic protein immunoreactivity was increased in LPS, but not in PTZ and LPS plus PTZ. These results indicate that LPS pretreatment reduces the passage of EB dye bound to albumin into the brain, at least partly, by increasing plasma NO and IL-6 levels during PTZ-induced epileptic seizures. We suggest that LPS may provide protective effects on the BBB integrity during epileptic seizures through transcellular pathway, since the paracellular route remained unaffected by LPS and LPS plus PTZ.

The exact incidence rate of subacute sclerosing panencephalitis (SSPE) in Turkey (and in Istanbul) is not known. We have conducted an active surveillance study to determine the epidemiological characteristics and the incidence rate of SSPE in Istanbul between the dates July 1, 2002 and July 1, 2004. We found that the incidence of SSPE in Istanbul is 2 per million. By logistic regression analysis, risk factors in SSPE development are determined as being at younger ages (OR: 1.199, 95%CI=1.047-1.372, P=0.009), living in crowded households (OR: 1.430, 95%CI=1.039-1.968, P=0.028), low education level of the mother (OR: 0.123, 95%CI=0.034-0.447, P=0.001), low household income (OR: 0.413, 95%CI=0.234-0.728, P=0.002), infant's being born out of Marmara region (Istanbul is in Marmara region of Turkey) (OR: 0.358, 95%CI: 0.172-0.746, P=0.006), infant's not being vaccinated against measles (OR: 0.495, 95%CI: 0.312-0.786), infant's having had measles before (OR: 0.235, 95%CI: 0.135-0.411). As a result, it is found in this study that SSPE is mostly related to having measles infection, and measles vaccination is found to be highly protective against SSPE. This is the first epidemiological study in SSPE from Turkey that conveys the incidence rate in Istanbul.

We report a family with four brothers affected by Lafora disease (LD). Mean age at onset was 19.5 years (range, 17-21). In all cases, the initial obvious symptoms were diffuse myoclonus and occasional generalized tonic-clonic seizures (GTCSs), followed by cognitive difficulties. Severity of myoclonus, seizure diaries, and neurologic and neuropsychological status were finally evaluated in March 2005. The duration of follow-up was >10 years for three subjects. Daily living activities and social interaction were preserved in all cases and, overall, the progression of the disease was slow. Genetic study revealed the homozygous mutation D146N in the EPM2B gene. We suggest that this mutation may be associated with a less severe LD phenotype.

This study is a field study with cross-section and case control conducted in the Kucukcekmece Region of Istanbul between June 1999 and February 2000. Four hundred and ninety three dwellings selected by a simple random sampling method were visited. From a population of 2187, 58 people, after filling in a questionnaire were suspected to have epilepsy. Following an interview, neurological examination and an electroencephalogram (EEG) 17 were diagnosed as having epilepsy. Lifetime epilepsy prevalence was 0.8%. 41.2% of the 17 epilepsy cases had partial epilepsy ( n= 7), 47.0% had generalized (n = 8) and in 11.8% seizures could not be classified ( n= 2). The risk factors for epilepsy in the control group ( n= 125) from the same region and those with epilepsy were investigated by means of logistic regression analyses. Educational status (odds ratio : 1.82, 95% confidence interval : 1.13-2.94; P= 0.01), profession (OR : 0.76, 95% CI : 0.60-0.97; P= 0.03), history of epilepsy in the family (OR : 0.67, 95% CI : 0.47-0.94; P= 0.02) were determined to be correlated with epilepsy. The results have drawn attention to the fact that individuals should be informed about epilepsy.

Experimental data indicate that acute hyperglycaemia can aggravate the consequences of epileptic seizures on the permeability of the blood-brain barrier (BBB). The purpose of this study was to examine the effects of chronic administration of alpha -tocopherol (vitamin E) and acute catalase administration on the disrupted BBB during experimentally pentylenetetrazole-induced status epilepticus in acute hyperglycaemic rats. The integrity of the BBB was tested using the Evans Blue (EB) dye extravasation. The concentration of EB dye was measured in four regions of the brain. Epileptic seizures induced a significant increase in EB dye extravasation in the brain regions compared with that of the groups of rats treated with saline, glucose, catalase and alpha -tocopherol (P< 0.01). The content of EB dye in the brain regions of animals in the acute hyperglycaemia plus epileptic group was higher than that of the saline, glucose, catalase, alpha -tocopherol and epileptic groups (P< 0.01). The increased EB dye transfer from blood to the brain in status epilepticus and acute hyperglycaemia plus status epilepticus was attenuated by the treatment with catalase and alpha -tocopherol. These data suggest that a partial reduction in the production of reactive oxygen species by catalase and alpha -tocopherol contributes to decreases in the content of EB dye across the BBB during pentylenetetrazole-induced status epilepticus in acute hyperglycaemic rats., (Copyright 2002 Elsevier Science Ltd.)