Headache in idiopathic/genetic epilepsy: Cluster analysis in a large cohort.

OBJECTIVE: The link between headache and epilepsy is more prominent in patients with idiopathic/genetic epilepsy (I/GE). We aimed to investigate the prevalence of headache and to cluster patients with regard to their headache and epilepsy features. METHODS: Patients aged 6-40 years, with a definite diagnosis of I/GE, were consecutively enrolled. The patients were interviewed using standardized epilepsy and headache questionnaires, and their headache characteristics were investigated by experts in headache. Demographic and clinical variables were analyzed, and patients were clustered according to their epilepsy and headache characteristics using an unsupervised K-means algorithm. RESULTS: Among 809 patients, 508 (62.8%) reported having any type of headache; 87.4% had interictal headache, and 41.2% had migraine. Cluster analysis revealed two distinct groups for both adults and children/adolescents. In adults, subjects having a family history of headache, ≥5 headache attacks, duration of headache ≥ 24 months, headaches lasting ≥1 h, and visual analog scale scores > 5 were grouped in one cluster, and subjects with juvenile myoclonic epilepsy (JME), myoclonic seizures, and generalized tonic-clonic seizures (GTCS) were clustered in this group (Cluster 1). Self-limited epilepsy with centrotemporal spikes and epilepsy with GTCS alone were clustered in Cluster 2 with the opposite characteristics. For children/adolescents, the same features as in adult Cluster 1 were clustered in a separate group, except for the presence of JME syndrome and GTCS alone as a seizure type. Focal seizures were clustered in another group with the opposite characteristics. In the entire group, the model revealed an additional cluster, including patients with the syndrome of GTCS alone (50.51%), with ≥5 attacks, headache lasting >4 h, and throbbing headache; 65.66% of patients had a family history of headache in this third cluster (n = 99). SIGNIFICANCE: Patients with I/GE can be clustered into distinct groups according to headache features along with seizures. Our findings may help in management and planning for future studies.

Efficacy, tolerability, and retention rates of zonisamide in older adult patients with focal-onset epilepsy: Experiences from two tertiary epilepsy centers.

OBJECTIVE: The objective of this study was to evaluate the efficacy, tolerability, and retention rates for zonisamide (ZNS) in older adult patients with focal-onset epilepsy. PATIENTS AND METHODS: Chart reviews of patients aged 60years and older with focal-onset epilepsy treated with ZNS in two tertiary epilepsy centers were analyzed retrospectively. RESULTS: Eighty-five patients (41 males, 44 females) aged over 60years (range: 60-81) with focal-onset epilepsy treated with ZNS were identified; 55.3% of the patients (n=47) were on monotherapy. The median and average doses of ZNS doses were 200mg/day (range: 100-400) and 212.9±84.2mg/day, respectively. With ZNS treatment, 67.1% of the patients (n=57) were seizure-free for a median of 28months (range: 10-56) whereas 20% (n=17) of the patients had seizures that were unresponsive to ZNS treatment. Best seizure control was achieved in patients with poststroke epilepsy; seizure freedom was 80% in this subgroup. Overall retention rate was found to be 83.5%. There was no significant relation between receiving poly- or monotherapy and discontinuation of ZNS (p=0.18). Thirty-two of the patients (37.6%) lost weight. Median weight loss was 8kg (range: 2-16). There was no significant correlation between weight loss and the administered doses of ZNS (r=0.34; p=0.12). CONCLUSION: Despite limitations due to the retrospective design of the study, the results show that ZNS is a well-retained drug with high efficacy in older adult patients with epilepsy.

QT interval alterations in epilepsy: A thorough investigation between epilepsy subtypes.

OBJECTIVES: Cardiac disturbances and rhythm abnormalities which potentially lead sudden unexpected death in epilepsy, have been extensively studied in focal epilepsies. However, studies including generalized epilepsies are scarce and it is not clear whether electrocardiogram parameters reflecting vulnerability to ventricular arrhythmias differ between these groups. METHODS: Medical records of patients who were followed in epilepsy department of a tertiary center between October 2015 and September 2016 were retrospectively reviewed. 66 generalized and 64 focal epilepsy patients with eligible electrophysiological data were analyzed. QTc interval, QTcd and other electrocardiographic indices were compared between patients with focal vs generalized epilepsy. Another analysis was performed in order to disclose any difference between patients with epilepsy (n:130) and psychogenic non-epileptic seizures. A two-tailed p value < 0.05 was considered significant. RESULTS: There was no difference in terms of QTc and QTcd between patients with focal and generalized epilepsy [median: 406 ms vs 404 ms, p = 0.119; and median: 46 ms vs 44 ms, p = 0.497, respectively]. However patients with epilepsy were found to have longer QTc and QTcd when compared to ones with psychogenic non-epileptic seizures (p = 0.035 and p < 0.001, respectively). CONCLUSION: Current findings demonstrate that patients with epilepsy have longer QTc and QTcd than patients with pure psychogenic non-epileptic seizures. Since there was no difference between patients with focal and generalized epilepsy; QTc interval, QTcd and potential susceptibility to cardiac arrhythmias as a result, could be a consequence of epilepsy itself regardless of origin.

Analysis of 24-hour heart rate variations in patients with epilepsy receiving antiepileptic drugs.

OBJECTIVE: The goal of the study described here was to evaluate interictal heart rate variability (HRV) in young patients with epilepsy, a patient population in whom sudden unexpected death in epilepsy (SUDEP) is known to be more common. METHODS: Twenty-four-hour ambulatory ECG Holter recordings of 37 patients (15-40 years old) and 32 healthy controls were compared. RESULTS: All of the time domain indices (SDNN, SDANN, RMSSD, and HRV triangular index) were significantly suppressed (P<0.001), and there was a marked reduction in parasympathetic tone (reduced HF(nu,)P<0.001) and an increase in sympathetic tone (increased LF(nu) and LF/HF ratio, P<0.001) in the patient group. Stepwise linear regression analysis revealed that polytherapy and epilepsy duration >10 years were independent variables associated with a reduction in SDNN. CONCLUSION: Our data suggest that the major determinants of suppressed SDNN are polytherapy and epilepsy duration >10 years. Analysis of spectral measures of frequency domain indices suggests that an increased sympathetic tone in association with a decreased parasympathetic tone may constitute the mechanism underlying SUDEP in young people with epilepsy.

Long-term effects of valproic acid on reproductive endocrine functions in Turkish women with epilepsy.

The long-term effects of valproic acid (VPA) on reproductive endocrine functions in women with epilepsy (WWE) were studied. Serum reproductive hormone concentrations, clinical findings and ovarian morphology were analyzed in 71 WWE who had been receiving antiepileptic drugs (AED) for a minimum of 2 years. Of the 71 WWE, polycystic ovarian syndrome (PCOS) (p = 0.011) and menstrual irregularities (p = 0.009) were found to be more prevalent in women receiving VPA treatment when compared to women on non-VPA treatment. There was no statistically significant dose or duration-related rise of risk for patients who developed PCOS and menstrual irregularities and those who were not on long-term VPA therapy. The lack of a duration-related reproductive dysfunction in this patient population may support the hypothesis of early occurring VPA-associated metabolic and endocrine changes.

Auditory P300 event-related potential in tobacco smokers.

The aim of this study was to elucidate the chronic effects of tobacco smoking on the P300, a neurophysiological index of cognitive function. Prospective study participants were recruited from a family medicine polyclinic. We selected 32 right-handed smokers who had smoked more than 15 cigarettes per day, by inhalation, for more than 2 years. The control population consisted of 32 right-handed, age-matched healthy individuals who had never smoked. Event-related potentials (ERPs) were recorded with the auditory "oddball" two-tone discrimination task. The data from the central (Cz) and frontal (Fz) electrodes were analyzed. The P300 and N1 amplitudes at Fz were lower in the study population compared to the control group. The early component of ERP, the measure of mental speed (N1) latency at Fz was prolonged in the study group compared to the controls, possibly because early cognitive processes such as sensory input or initial encoding of sensory information were delayed in this group. For those who smoke, a decreased N1 amplitude might indicate delayed information processing and possibly short-term memory disturbance. Thus, chronic tobacco smoking may produce prefrontal cognitive dysfunction.

Adjunctive lacosamide treatment for adult focal-onset epilepsy: focus on comorbid intellectual/developmental disorders and differing responses.

BACKGROUND: Data regarding lacosamide treatment as an adjunctive therapy in patients representative of a focal-onset epilepsy population including those with and without intellectual/developmental disorders (IDDs) are limited. PURPOSE: To evaluate the retention rates of lacosamide in focal-onset epilepsy patients with and without IDD. PATIENTS AND METHODS: We retrospectively reviewed all consecutive electronic and paper medical records of patients diagnosed with focal-onset epilepsy who were treated with lacosamide in two tertiary epilepsy centers. RESULTS: One hundred and thirty-six patients who met the inclusion criteria were studied. Number of patients with IDD was 46 (33.8%). Median lacosamide dose was 300 mg/day. A total of 39 patients (28.7%) experienced side effects, and 22 of them (16.2%) discontinued lacosamide. The 1-, 2-, and 3-year retention rates of lacosamide in patients with IDD were 68%, 62%, and 53%, respectively. Kaplan-Meier survival analysis showed that the retention rates were significantly lower in patients with IDD when compared to patients without IDD (P=0.04). Cox regression analysis showed that concomitant use of sodium channel blocker antiepileptic drugs (AEDs) was the only independent predictor of retention rate of lacosamide treatment (P=0.03). In the subgroup of patients with IDD, the analysis was performed again and the number of background AEDs was the only predictor for the retention rate of lacosamide (P=0.04). CONCLUSION: When compared to patients without IDD, retention rates of lacosamide adjunctive therapy were lower in patients with IDD. However, these rates were higher than the rates suggested with previously registered AEDs including lamotrigine, levetiracetam, and topiramate. Therefore, irrespective of having comorbid IDD, we might suggest that lacosamide is a well-retained drug with a high efficacy profile in patients with focal-onset epilepsy.

Retrograde flow in the left inferior petrosal sinus and blood steal of the cavernous sinus associated with central vein stenosis: MR angiographic findings.

BACKGROUND AND PURPOSE: We attempted to identify the cause of abnormal venous flow seen during arterial MR angiography in the inferior petrosal sinus by use of in three female patients (aged 51, 48, and 70 years, respectively). METHODS: Arterial 3D time-of-flight MR angiography was performed with a tilted optimized nonsaturating excitation pulse sequence (TR/TE, 31/7; flip angle, 20 degrees; section thickness, 65 mm; effective thickness, 1 mm; number of sections, 1 to 2); no magnetization transfer pulse sequence was used. Contrast-enhanced 3D MR angiography of the neck was performed with a 3D fast low-angle shot pulse sequence (TR/TE, 4.6/1.8; flip angle, 40 to 45 degrees; section thickness, 80 mm; intersection gap, 1.5 mm; acquisition matrix, 180 x 256; acquisition time, 27 s) on a system with a whole-body coil. RESULTS: In all three patients, 3D time-of-flight MR angiography revealed abnormal vascular signal originating from the left cavernous sinus, continuing through the inferior petrosal sinus, and ending in the proximal internal jugular vein at the jugular bulb level. Abnormal vascular signal at the jugular bulb, sluggish flow and flow-related enhancement in the left internal jugular vein, and signal void in the contralateral jugular vein were noted. Contrast-enhanced delayed-phase MR angiography showed stenosis in the left brachiocephalic vein in all patients. CONCLUSION: High signal intensity noted at the inferior petrosal sinus resulted from retrograde flow. Retrograde flow was due to blood stealing from the internal jugular vein toward the cavernous sinus because of venous stenosis in the brachiocephalic vein.

Dural carotico-cavernous fistula: pre and postembolization appearances of bone-subtracted CT angiography.

Digital subtraction angiography (DSA) is the best method of evaluating carotid cavernous fistulas (CCF). DSA, however, has the disadvantage of being an invasive procedure. Computerized tomography (CT) angiography which is noninvasive, have been shown to provide more information about the size and location of fistulas. As a new method, Bone-Subtraction CT Angiography (BSCTA), than conventional CT angiography, is a method that improves the detection and interpretation of vascular lesions near to the cavernous segment of carotid artery. In this case report, we report a case of a dural carotico-cavernous fistula (CCF), appearances of pre and postembolization BSCTA images, confirmed by on DSA. As far as we know, CCF demonstrated by BSCTA has not been reported yet.

Ocular changes associated with topiramate.

PURPOSE: To determine the changes in refractive error, and the cornea, anterior chamber, and retina induced by topiramate. METHODS: The study included 76 eyes of 38 patients that began to use topiramate due to migraine. Following ophthalmological examination, all of the patients underwent central corneal thickness (CCT), anterior chamber volume (ACV), anterior chamber depth (ACD), and anterior chamber angle (ACA) measurement using a Scheimpflug camera, as well as macular thickness, retinal and retinal nerve fiber layer thickness (RNFLT) measurements using optical coherence tomography (OCT). These procedures were repeated 15, 30, and 90 days after the initiation of topiramate therapy. RESULTS: The median refractive error value showed a statistically significant increase from -0.25 diopters (D) to -0.62 D at the 90th day follow-up (P < 0.001). Mean CCT was 570.56 µm before treatment and increased to 573.69 µm at the 15th day follow-up, 575.31 µm at the 30th day follow-up, and 574.56 µm at the 90th day follow-up; however, these changes were not statistically significant. Mean ACV, ACD, and ACA did not exhibit statistically significant changes. Mean retinal thickness (RT) increased during the treatment from 263.46 µm to 271.60 µm, which was not statistically significant. The initial mean RNFLT was 100.56 ± 15.36 µm and significantly increased to 110.2 ± 8.41 µm and 111.03 ± 14.59 µm at the 30th and 90th day follow-ups, respectively (P = 0.01 and P = 0.004, respectively). CONCLUSIONS: During the 3-month follow-up of patients using topiramate 50 mg d(-1) significant myopic shift and an increase in RNFLT were observed. Further studies are warranted in order to assess the effects of topiramate when used long term and at higher doses.

Anthropometric indexes, insulin resistance, and serum leptin and lipid levels in women with cryptogenic epilepsy receiving topiramate treatment.

We aimed to investigate the effects of topiramate monotherapy on anthropometric indexes, insulin resistance, and serum leptin and lipid levels in 33 premenopausal women (mean age+/-standard deviation: 26.7+/-7.1years) with cryptogenic epilepsy. Body mass index (BMI), waist circumference and serum leptin, insulin and lipid levels were measured at baseline and at 6months after initiation of topiramate. We found reductions in BMI (p<0.001), waist circumference (p<0.001) and serum high-density lipoprotein (HDL) cholesterol levels (p=0.011). We also found significant improvements in insulin resistance (p=0.023), but not in serum leptin levels (p=0.45). Our results suggest that topiramate treatment in women with epilepsy is associated with reduced BMI and waist circumference and improvement in insulin resistance; however, according to our data, topiramate treatment is also associated with lower HDL cholesterol levels, which may substantially increase vascular disease.

Evaluation of cardiac repolarization indices in well-controlled partial epilepsy: 12-Lead ECG findings.

PURPOSE: To evaluate the cardiac repolarization indices in terms of QT intervals in patients with well-controlled partial epilepsy. METHODS: Seventy-six adult patients with well-controlled partial epilepsy and 66 healthy controls were enrolled into the study. 12-Lead ECGs were obtained from all participants. Corrected QT (QTc) intervals including maximum QTc (QTmaxc), minimum QTc (QTminc) and QTc dispersion (QTcd) were calculated. RESULTS: QTmaxc and QTcd intervals were significantly longer in the epilepsy group when compared to control group (439+/-27 ms vs. 422+/-25 ms, p<0.001 and 55+/-18 ms vs. 41+/-18 ms, p<0.001). The proportion of patients with pathologically prolonged QTcd intervals (>50 ms) was significantly higher in the epilepsy group (25 of 76 vs. 7 of 66, p=0.002). QTmaxc was significantly correlated with age (beta=0.29, p=0.012) after adjusting for gender, body mass index and duration of epilepsy. No correlation was observed between the duration of epilepsy and any of the QT intervals. There were no significant differences between the subgroups regarding QT intervals according to the etiology of the seizures (symptomatic/cryptogenic), being on mono- or polytherapy and treatment regimens (carbamazepine/non-carbamazepine). CONCLUSION: The results highlight the importance of cardiac evaluation even in patients with well-controlled epilepsy. 12-lead ECG recordings might help to uncover serious cardiovascular events.

Neuro-Behçet's syndrome presenting with features mimicking acute tuberculous meningitis.

Behçet's disease is an inflammatory disease that can involve multiple systems. Here, we describe a case of neuro-Behçet's syndrome presenting with features mimicking acute tuberculous meningitis. Behçet's disease should be considered in the differential diagnosis of a meningeal syndrome unless a viral or bacterial agent is demonstrated.

Bilateral mesial temporal sclerosis and kernicterus.

Two children with mental retardation, choreoathetosis, dystonia, and muscle rigidity are reported. They had a history of severe hyperbilirubinemia after birth as a result of Rh isoimmunization. The history and clinical picture suggested the diagnosis of kernicterus. The magnetic resonance imaging examination showed a bilateral signal intensity increase in the globus pallidus on T2-weighted images. Additionally, our patients showed symmetric bilateral hyperintensity and volume loss in the hippocampus, which is known to be another characteristic area of bilirubin deposition in kernicterus.

Correlation between tissue lactate levels and electroencephalogram in evaluating the severity of experimental head trauma.

OBJECTIVE: The objective of this study was to develop an electroencephalographic grading scale for evaluating the severity of head trauma and assessing the correlation of this scale with brain tissue lactate concentrations. DESIGN: Animal experiment. SETTING: Animal research laboratory in a university hospital. SUBJECTS: Thirty New Zealand rabbits were divided into three groups. INTERVENTIONS: Rabbits were anesthetized, and bilateral frontoparietal craniectomy was performed. An electroencephalogram was recorded over the dura from both sides. After electroencephalographic recording, unilateral trauma was produced by using the weight drop method with a calculated force of 400 g.cm and 800 g.cm in group 2 (n = 10) and group 3 (n = 10), whereas in group 1 (n = 10) only craniectomy was performed. Electroencephalographic recording was repeated 60 mins after trauma or craniectomy, and cortical tissue samples were resected from both sides to evaluate tissue lactate concentrations in all three groups. MEASUREMENTS AND MAIN RESULTS: Electroencephalographic recordings from both sides of the brain were evaluated together by using a 6-point scale (1 = best to 6 = worst) that was based on the presence or absence of electroencephalographic activity and the decrease in amplitude or frequency band of the electroencephalogram. Lactate was measured in resected tissue by using spectrophotometric enzymatic methods. One-way analysis of variance for repeated measures, Bonferroni-adjusted paired Student's -test, Kruskal Wallis analysis of variance, Bonferroni-adjusted Mann-Whitney-U, and Spearman's correlation tests were used as appropriate for statistical analysis. We considered p<.05 to be significant. The difference in lactate concentrations was significant between the three groups ( p<.05). Electroencephalographic grades were significantly different between the pretraumatic and posttraumatic recordings ( p<.05) and between the three groups after craniectomy or trauma ( p<.001). There was a positive high correlation between lactate concentrations and electroencephalographic grades. CONCLUSIONS: Tissue lactate concentrations and electroencephalograhic grades change with the severity of the trauma, and there is a strong positive correlation between tissue lactate concentrations and electroencephalographic grades.