A cross-sectional survey among physicians on internet use for epilepsy-related information.

OBJECTIVE: We investigated views towards the Internet in a sample of Italian healthcare specialists involved in epilepsy field, to identify factors associated with the attitude of being influenced by information found on the Internet. METHODS: This study was a self-administered survey conducted in a group of members of the Italian Chapter of the International League Against Epilepsy (ILAE) in January 2018. RESULTS: 184 questionnaires were analyzed. 97.8 % of responders reported to seek online information on epilepsy. The Internet was most frequently searched to obtain new information (69.9 %) or to confirm a diagnostic or therapeutic decision (37.3 %). The influence of consulting the Internet on clinical practice was associated with registration to social network(s) (OR: 2.94; 95 %CI: 1.28-6.76; p = 0.011), higher frequency of Internet use (OR: 3.66; 95 %CI: 1.56-9.21; p = 0.006) and higher confidence in reliability of online information (OR: 2.61; 95 %CI: 1.09-6.26; p = 0.031). No association was found with age, sex, years in epilepsy practice or easiness to find online information. CONCLUSION: Internet is frequently used among healthcare professionals involved in the epilepsy to obtain information about this disease. The attitude of being influenced by the Internet for diagnostic and/or therapeutic decisions in epilepsy is independent on age and years of experience in epilepsy, and probably reflects an individual approach towards the Web.

Psychotic disorder and focal epilepsy in a left-handed patient with chromosome XYY abnormality.

OBJECTIVE: To discuss the relationship between XYY chromosome abnormality, psychiatric disorders and epilepsy. METHOD: Single case report. RESULTS: A 34-year-old man with 47, XYY karyotype and normal intelligence was followed-up at a neuropsychiatric clinic for over 30 years. He was first seen at age 3 years with a history of delayed motor and language development and an immunodeficiency syndrome. At age 8 years he developed refractory focal epilepsy, and in late adolescence he started to exhibit increasingly prominent obsessive thoughts, paranoid ideation, and aggressive sexual fantasies and behaviour. CONCLUSIONS: When interpreted within the context of previous literature reports, this case suggests a pathophysiological link between XYY chromosome abnormality, characteristic psychiatric symptoms and epilepsy disorder.

Memory guided saccades in mesial temporal lobe epilepsy with hippocampal sclerosis.

OBJECTIVE: Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) may involve extrahippocampal areas of structural and functional damage. The incidence and the features of this damage are still a matter of debate and vary depending on the method applied. Memory guided saccades (MGSs) with a memorization delay longer than 20s can be used reliably to evaluate the parahippocampal cortex. METHODS: MGSs with 3 and 30s memorization delays were recorded with the search coil technique in six patients affected by right MTLE-HS, and in 13 healthy controls. RESULTS: The patients were not able to reduce the MGSs residual amplitude error after the first saccade with a 30s memorization delay. This finding was more evident with leftward saccades. CONCLUSIONS: MGS abnormalities suggested the functional involvement of the right parahippocampal cortex in most of the patients with MTLE-HS, and this supports the clinical and anatomopathological heterogeneity of the disease. SIGNIFICANCE: MGSs can be used in patients with right MTLE-HS to detect a possible functional involvement of the ipsilateral parahippocampal cortex.

Epileptic skew deviation.

We describe a 43-year-old neurologically intact patient who reported episodes of diplopia and oscillopsia associated with a right-beating nystagmus and a skew deviation. These symptoms and signs were related to a left posterior epileptic EEG discharge. We suggest that these ocular motor signs derived from an ictal activation of the vestibular cortex, which in turn activated descending projections to the vestibular nuclei, leading to both a dynamic (right-beating nystagmus) and a static (skew deviation) vestibular imbalance.

Familial hemiplegic migraine versus migraine with prolonged aura: an uncertain diagnosis in a family report.

Four of five members of a family complained of repeated attacks of hemiplegic migraine, migraine with aura of different types, or migraine without aura. The hemiplegia always outlasted the headache and was often accompanied by altered consciousness, aphasia, and, in one patient, coma; in this latter patient, the ictal EEG, recorded during two attacks, showed delta activity in the hemisphere contralateral to the hemiplegia. At least 2 months after their latest attacks, three patients showed dyscalculia, attentional disturbances, and impaired long-term verbal memory on neuropsychologic assessment. There were no cognitive disturbances in the unaffected relative. The severity of cognitive impairment appears to be correlated with migraine history. We attempt to classify these cases according to the criteria of the International Headache Society.

Sleep patterns in patients with late onset partial epilepsy receiving chronic carbamazepine (CBZ) therapy.

A night-time polygraphic sleep recording was performed in 14 patients with late onset partial epilepsy receiving chronic carbamazepine monotherapy. All patients had unstable nocturnal sleep patterns as indicated by significantly altered sleep continuity parameters compared with normal controls. Patients with poor seizure control tended to show greater alterations of sleep stability compared to patients in complete clinical remission but the difference failed to reach statistical significance. Epileptic patients also showed less REM sleep and longer REM latencies compared with normal controls, the most altered REM values being observed in patients with poor seizure control. These data confirm that polygraphic sleep alterations are seen in patients with symptomatic focal epilepsy and indicate that these abnormalities occur irrespective of seizure recurrence.

Effects of valproate, phenobarbital, and carbamazepine on sex steroid setup in women with epilepsy.

Serum levels of sex-hormones, sex-hormone binding globulin, gonadotropin, and prolactin were evaluated during the follicular and the luteal phases in 65 women with epilepsy and in 20 healthy controls. Twenty-one patients were treated with sodium valproate (VPA), 21 with phenobarbital (PB), and 23 with carbamazepine (CBZ). VPA does not stimulate liver microsome enzymes, whereas PB and CBZ do. Patients on VPA therapy showed higher body weight and body mass index, but no significant differences in hirsutism score, or in ovary volume or polycystic ovary prevalence (at ultrasound examination). Estradiol levels were lower in all patient groups than in healthy controls in the follicular but not in the luteal phases. VPA affected luteal progesterone surge in 63.6% of cases. This effect was significantly lower in the CBZ and PB groups. Furthermore, increases in testosterone and delta 4-androstenedione levels and in free androgen index, along with a higher luteinizing hormone-follicle-stimulating hormone ratio in the luteal phase, were observed in women treated with VPA. Although sex-hormone binding globulin levels were higher in CBZ and PB than in VPA-treated patients, the differences were not significant because of the wide dispersion of the carrier protein levels. Inducer antiepileptic drugs decreased dehydroepiandrosterone sulfate levels, which remained unchanged during VPA treatment. No significant differences occurred in basal gonadotropin and prolactin levels.

Daytime sleepiness in epileptic patients on long-term monotherapy: MSLT, clinical and psychometric assessment.

A multiparametric investigation of daytime sleepiness was carried out in 10 patients with a generalized epilepsy treated by phenobarbital, 10 with a cryptogenic partial epilepsy treated by carbamazepine and 10 healthy controls. After a standard ambulatory night-time polysomnography, an objective and subjective estimate of daytime sleepiness was made in each subject by means of the Multiple Sleep Latency Test (MSLT) and visual analogue rating scale (VARS), respectively. Furthermore, a parallel assessment of mood and cognitive tasks involving attention and psychomotor speed was also carried out. The data show that patients on chronic treatment with phenobarbital have a greater daytime sleep tendency and they show a worse score at the digit symbol substitution test, than patients on carbamazepine and healthy controls.

Drug withdrawal in patients with epilepsy: prognostic value of the EEG.

The role of the inter-ictal EEG in predicting seizure relapse after antiepileptic drug withdrawal (AED-W) is unclear. A prospective study on AED-W is in progress. This trial includes routine and sleep EEG recordings every 3 and 6 months, respectively, at each step of the drug discontinuation and periodically during follow-up. Data obtained for 136 patients (mean age 23.2 years; 63 with Idiopathic Generalized Epilepsy IGE, 73 with Partial Cryptogenic or Symptomatic Epilepsy PE; without associated neuropsychiatric handicap; with at least 1 year of follow-up after AED-W) were analysed. EEG recordings from seizure onset were available for all patients. Data were analysed separately in IGE and PE patients. The presence of inter-ictal epileptiform abnormalities (IEAs) at the seizure onset and just before AED-W does not seem to predict the AED-W outcome. However, results indicate an association between persisting and increased IEAs during AED-W and a higher relapse rate in both groups, which was statistically significant in the IGE patients.

Nocturnal partial seizures and arousals/awakenings from sleep: an ambulatory EEG study.

The architecture of nocturnal sleep in twenty subjects (9 males, 11 females, mean age 27 years) affected by partial cryptogenic epilepsy was investigated by means of ambulatory EEG (A-EEG) recording performed at home. The study aimed in particular to ascertain the immediate effects of nocturnal partial epileptic seizures on sleep stability and continuity. Data for a total of 49 recorded seizures indicate that 72% of the partial seizures which occurred during sleep were followed by arousal and awakening, and that sleep interruption lasted significantly longer when the seizure occurred between 4 and 7 a.m.

Comparative pharmacokinetics and pharmacodynamics of eterobarbital and phenobarbital in normal volunteers.

The comparative pharmacokinetics and pharmacodynamics of single oral doses of eterobarbital (N,N'-dimethoxymethylphenobarbital, DMMP, 400 mg) and phenobarbital (200 mg) were evaluated in a double-blind study in 8 normal volunteers. Following administration of DMMP, no unchanged drug could be detected in serum. The active monomethoxymethyl metabolite (MMP) appeared rapidly in the circulation but its concentration remained generally low and declined below the limit of detection (0.5 micrograms/ml) usually before 9.5 h. Serum levels of DMMP-derived PB increased slowly and reached a peak between 24 and 48 h in most cases. One subject showed an atypical pharmacokinetic profile, characterized by relatively high levels of MMP and a delayed appearance of low levels of PB. After administration of PB, serum drug levels peaked within 1.5 h and remained, at all sampling times, higher than those observed after intake of DMMP. Compared with DMMP, PB induced greater sedative effects as assessed by visual analogue rating scale, critical flicker fusion frequency and multiple sleep latency tests.

Vigabatrin in the treatment of epilepsy: a long-term follow-up study.

Twenty-five adult epileptic patients who had shown a satisfactory clinical response to add-on vigabatrin under placebo-controlled conditions continued on long-term treatment for up to 47 months (median 22 months). The initially favourable therapeutic response was generally maintained throughout the observation period with an overall good clinical tolerance. No evidence of neurotoxicity was detected by multimodal evoked potentials monitoring.

A multiparametric investigation of daytime sleepiness and psychomotor functions in epileptic patients treated with phenobarbital and sodium valproate: a comparative controlled study.

Subjective and objective measures of daytime sleepiness and psychomotor function were determined in normal control subjects and in epileptic patients on chronic monotherapy with phenobarbital or valproate (n = 10 in each group). All patients had primary generalized epilepsy with a normal resting EEG and were seizure-free for at least 1 year. After nocturnal polysomnographic recording, each subject was evaluated at 2 h intervals between 10:00 and 16:00 h by using multiple sleep latency tests (MSLT), a visual analogue rating scale for alertness (VARS), an anxiety scale (STAI-X1) and a battery of psychomotor tests. Nocturnal sleep parameters before daytime assessment were comparable in the 3 groups. At MSLT, patients on phenobarbital showed a shorter mean sleep latency (9.0 +/- 1.7 min) compared with the valproate group (12.5 +/- 1.3 min) and controls (12.9 +/- 1.2 min), though within-group variability was considerable. Compared with controls, patients on phenobarbital showed longer motor movement times, impaired attention (cancellation test, CT), reduced processing speed (digit-symbol substitution, DSS) and a trend towards lower critical flicker fusion threshold. Patients on valproate showed some impairment in attention and a trend towards longer motor movement time. In patients, no correlation was found between assessed parameters and serum drug concentrations, which were 19.3 +/- 1.7 micrograms/ml for phenobarbital and 85.7 +/- 4.7 micrograms/ml for valproic acid.

Efficacy and safety of topiramate in refractory epilepsy: a long-term prospective trial.

The effects of topiramate in 15 patients with drug refractory epilepsy or Lennox-Gastaut syndrome were assessed in an open, add-on prospective study. After a follow-up of 14-21 months, six patients are still on topiramate (mean dosage 583 mg/day, range 400-800 mg/day), and nine have discontinued treatment because of adverse events (n = 6), inefficacy (n = 2) or poor compliance (n = 1). Nine patients (69%) continued to have > or = 50% reduction in seizure frequency during the last two months of treatment, and one has been seizure-free for the last 19 months. The most common adverse events were somnolence, weight loss, mental slowing, fatigue, ataxia and irritability. Most of these events were reversible, but withdrawal of treatment was required in six cases as a result of ataxia (two patients), somnolence, metabolic acidosis, irritability or psychotic symptoms (one patient each). It is concluded that topiramate is a valuable agent for long-term management of refractory epilepsy.

Partial epileptic seizures of different origin variably affect cardiac rhythm.

PURPOSE: The present study was aimed at evaluating electrocardiographic (ECG) changes associated with partial epileptic seizures without seizure activity secondarily generalized. METHODS: We assessed heart rate (HR) changes occurring during 100 partial epileptic seizures, as recorded by ambulatory EEG-ECG in 50 outpatients. Consecutive R-R intervals were measured for the 30 s immediately preceding the onset and for the first 10-s period of discharge. In addition, HR was sampled at 10-s intervals during EEG paroxysmal discharge and for 1 min after the end of discharge. RESULTS: The highest and lowest respective HR peaks achieved during these seizures were 186 and 44 beats/ min. Analysis of the R-R intervals during the first 10-s period of EEG discharge showed a significant early HR increase in 49% of the seizures; the corresponding figure for an early HR reduction was 25.5%. Eighty percent of the seizures showing an early HR decrease were of temporal lobe origin. No severe cardiac arrhythmias were noted during the seizures. CONCLUSIONS: Our data suggest that an early HR decrease is more probable in temporal lobe seizures than in seizures of other origin. An accurate HR measurement, focused on discharge onset, may provide both a reliable way of evaluating the possible effect of partial seizures on HR and valuable information about the cerebral sites involved in the control of cardiac rhythm.

Vigabatrin in the treatment of epilepsy: a double-blind, placebo-controlled study.

The efficacy and tolerability of vigabatrin (gamma-vinyl GABA, GVG), given as add-on therapy to 23 adult outpatients with severe drug-resistant epilepsy (17 with partial seizures), were studied using a double-blind, placebo-controlled, crossover design. The study consisted of two 7-week periods during which vigabatrin and placebo were administered in random sequence. Dosage was 1.0 g twice daily for patients weighing less than or equal to 65 kg and 1.5 g twice daily for patients weighing greater than 65 kg. Three patients were dropped from the study, two for reasons unrelated to treatment and one because of the appearance of vertigo, headache, dysarthria, and ataxia, which subsided rapidly when vigabatrin was stopped (3 g daily). Sixteen of the 20 patients available for analysis showed a decrease in the total number of seizures as compared with the placebo period. Of these, 12 showed a greater than 50% reduction in seizure frequency and 4 of the 12 showed a greater than 75% reduction. Both the total number of seizures and the number of partial seizures were significantly reduced by vigabatrin (p less than 0.01). Only in the patient who dropped out were severe adverse effects seen. The most frequently reported unwanted effect was mild drowsiness, which developed in seven patients on vigabatrin and in one on placebo. Positive effects, however, were also seen with six patients who reported an improved sense of well-being while receiving vigabatrin as compared with only 1 during the placebo period. No consistent changes in electrocardiogram (ECG), electroencephalogram (EEG), and visual-, auditory-, and somatosensory-evoked potentials were seen during the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of vigabatrin (gamma-vinyl-GABA) on visual, brainstem auditory and somatosensory evoked potentials in epileptic patients.

Visual (V), somatosensory (S) and brainstem auditory (BA) evoked potentials (EPs) were determined in 22 epileptic patients, mostly with partial seizures, who received add-on treatment with vigabatrin (1-3 g/day, stratified according to body weight) and placebo, each given for 7 weeks according to a double-blind, randomized cross-over design. At pretreatment assessment, BAEPs and SEPs were found to be within normal limits in most of the patients tested, while for VEPs several abnormal responses were found, including a marked prolongation of P100 latency values in the majority of cases. None of the EP parameters examined was significantly influenced by vigabatrin treatment. These results support the evidence that enhancement of GABA-ergic transmission does not substantially affect the functional state of afferent sensory pathways as assessed by EP analysis. The significance of these findings with respect to the safety of vigabatrin therapy is discussed.

Time-dependent pharmacodynamic effects of phenobarbital in humans.

The relationship between the serum concentration of phenobarbital and its pharmacodynamic effects was assessed in a double-blind controlled study in eight normal volunteers who were given single oral doses of phenobarbital (200 mg) and placebo according to a randomized cross-over design. Compared with the placebo session, phenobarbital was found to induced CNS-depressing effects as assessed by visual analogue rating scales (VARS) and critical flicker fusion tests (CFF), whereas no significant effects were detected on choice reaction times, tappings, and digit symbol substitutions. There was a clear-cut dissociation between the time course of serum phenobarbital levels, which remained at a plateau throughout most of the period of observation (up to 72 h) and its subjective (VARS) and objective (CFF) effects, which could be documented only for up to 9 h after administration. These data suggest that pharmacodynamic tolerance develops rapidly even after a single oral dose of the drug. Multiple Sleep Latency Tests (MSLTs) were also performed in the same subjects and showed that phenobarbital increases diurnal drowsiness and attenuates the circadian variation in drowsy state that is seen under control conditions. MLSTs appeared to be superior to other tests in documenting the sedative effects of the barbiturate.