NMDA receptor binding in focal epilepsies.

OBJECTIVE: To demonstrate altered N-methyl-d-aspartate (NMDA) receptor availability in patients with focal epilepsies using positron emission tomography (PET) and [(18)F]GE-179, a ligand that selectively binds to the open NMDA receptor ion channel, which is thought to be overactive in epilepsy. METHODS: Eleven patients (median age 33 years, 6 males) with known frequent interictal epileptiform discharges had an [(18)F]GE-179 PET scan, in a cross-sectional study. MRI showed a focal lesion but discordant EEG changes in two, was non-localising with multifocal EEG abnormalities in two, and was normal in the remaining seven patients who all had multifocal EEG changes. Individual patient [(18)F]GE-179 volume-of-distribution (VT) images were compared between individual patients and a group of 10 healthy controls (47 years, 7 males) using Statistical Parametric Mapping. RESULTS: Individual analyses revealed a single cluster of focal VT increase in four patients; one with a single and one with multifocal MRI lesions, and two with normal MRIs. Post hoc analysis revealed that, relative to controls, patients not taking antidepressants had globally increased [(18)F]GE-179 VT (+28%; p<0.002), and the three patients taking an antidepressant drug had globally reduced [(18)F]GE-179 VT (-29%; p<0.002). There were no focal abnormalities common to the epilepsy group. CONCLUSIONS: In patients with focal epilepsies, we detected primarily global increases of [(18)F]GE-179 VT consistent with increased NMDA channel activation, but reduced availability in those taking antidepressant drugs, consistent with a possible mode of action of this class of drugs. [(18)F]GE-179 PET showed focal accentuations of NMDA binding in 4 out of 11 patients, with difficult to localise and treat focal epilepsy.

In-depth performance analysis of an EEG based neonatal seizure detection algorithm.

OBJECTIVE: To describe a novel neurophysiology based performance analysis of automated seizure detection algorithms for neonatal EEG to characterize features of detected and non-detected seizures and causes of false detections to identify areas for algorithmic improvement. METHODS: EEGs of 20 term neonates were recorded (10 seizure, 10 non-seizure). Seizures were annotated by an expert and characterized using a novel set of 10 criteria. ANSeR seizure detection algorithm (SDA) seizure annotations were compared to the expert to derive detected and non-detected seizures at three SDA sensitivity thresholds. Differences in seizure characteristics between groups were compared using univariate and multivariate analysis. False detections were characterized. RESULTS: The expert detected 421 seizures. The SDA at thresholds 0.4, 0.5, 0.6 detected 60%, 54% and 45% of seizures. At all thresholds, multivariate analyses demonstrated that the odds of detecting seizure increased with 4 criteria: seizure amplitude, duration, rhythmicity and number of EEG channels involved at seizure peak. Major causes of false detections included respiration and sweat artefacts or a highly rhythmic background, often during intermediate sleep. CONCLUSION: This rigorous analysis allows estimation of how key seizure features are exploited by SDAs. SIGNIFICANCE: This study resulted in a beta version of ANSeR with significantly improved performance.

Early serial EEG in hypoxic ischaemic encephalopathy.

OBJECTIVES: To perform early serial EEGs in infants with hypoxic ischaemic encephalopathy (HIE) and compare the findings with neurodevelopmental outcome. METHODS: Nine full-term neonates with HIE had simultaneous video-EEG polygraphic studies within 8 h of birth. The EEG was repeated at 12-24 h intervals. All surviving infants had a neurodevelopmental assessment at 1 year. RESULTS: Two infants had a normal or mildly abnormal EEG within 8 h of birth and neurodevelopmental outcome was normal. Seven infants had severely depressed background activity in the first 8 h of life. In 3 infants the EEG activity recovered within 12-24 h showing continuous activity with no or only minor abnormalities. All these infants had a normal outcome. The remaining 4 infants, who also had an initially inactive recording, subsequently developed severe background abnormalities. At follow-up, two infants had died and the remainder developed major neurological sequelae. CONCLUSIONS: Early EEG is an excellent prognostic indicator for a favourable outcome if normal within the first 8 h of life and for a poor outcome if the background activity continues to be inactive or grossly abnormal beyond 8-12 h of life. However, an inactive or very depressed EEG within the first 8 h of life can be associated with good outcome if the EEG activity recovers within 12 h.

Comparison of EEG, MRI and PET in reading epilepsy: a case report.

The pathophysiological and neuroanatomical bases of reading epilepsy (RE) are unclear. We performed video-EEG, high quality MRI and [11C]diprenorphine PET in a patient with RE to detect structural and functional abnormalities. EEG showed multifocal seizure onset bilaterally in temporal and fronto-central regions. MRI was normal, whereas [11C]diprenorphine PET revealed peri-ictal opioid binding decreases in both temporal lobes and the left frontal lobe. These findings confirm that RE is due to abnormal activity in the network subserving reading.

Phenobarbitone, neonatal seizures, and video-EEG.

AIMS: To evaluate the effectiveness of phenobarbitone as an anticonvulsant in neonates. METHODS: An observational study using video-EEG telemetry. Video-EEG was obtained before treatment was started, for an hour after treatment was given, two hours after treatment was given, and again between 12 and 24 hours after treatment was given. Patients were recruited from all babies who required phenobarbitone (20-40 mg/kg intravenously over 20 minutes) for suspected clinical seizures and had EEG monitoring one hour before and up to 24 hours after the initial dose. An EEG seizure discharge was defined as a sudden repetitive stereotyped discharge lasting for at least 10 seconds. Neonatal status epilepticus was defined as continuous seizure activity for at least 30 minutes. Seizures were categorised as EEG seizure discharges only (electrographic), or as EEG seizure discharges with accompanying clinical manifestations (electroclinical). Surviving babies were assessed at one year using the Griffiths neurodevelopmental score. RESULTS: Fourteen babies were studied. Four responded to phenobarbitone; these had normal or moderately abnormal EEG background abnormalities and outcome was good. In the other 10 babies electrographic seizures increased after treatment, whereas electroclinical seizures reduced. Three babies were treated with second line anticonvulsants, of whom two responded. One of these had a normal neurodevelopmental score at one year, but the outcome for the remainder of the whole group was poor. CONCLUSION: Phenobarbitone is often ineffective as a first line anticonvulsant in neonates with seizures in whom the background EEG is significantly abnormal.

Effect of lamotrigine on cognition in children with epilepsy.

BACKGROUND: Lamotrigine does not affect cognition in healthy adult volunteers or adult patients with epilepsy, but its effect on cognition in children is uncertain. OBJECTIVE: To compare the effect of lamotrigine and placebo on cognition in children with well-controlled or mild epilepsy. METHOD: In a double-blind, placebo-controlled, crossover study, 61 children with well-controlled or mild epilepsy were randomly assigned to add-on therapy with either lamotrigine followed by placebo or placebo followed by lamotrigine. Each treatment phase was 9 weeks, the crossover period 5 weeks. A neuropsychological test battery was performed during EEG monitoring at baseline and at the end of placebo and drug phases. The paired Student' t test was used for statistical analysis for neuropsychological data (two tailed) with a p value of 0.01 considered significant. Carryover and period effect were analyzed with generalized linear modeling (SPSS 10). RESULTS: Forty-eight children completed the study. Seizure frequency was similar during both treatment phases. No significant difference was found in continuous performance, binary choice reaction time, verbal and nonverbal recognition, computerized visual searching task, verbal and spatial delayed recognition, and verbal and nonverbal working memory between placebo and lamotrigine treatment phase. There was no significant carryover and period effect when corrected for randomization. CONCLUSION: Lamotrigine exhibits no clinically significant cognitive effects in adjunctive therapy for children with epilepsy.

Second-line anticonvulsant treatment of neonatal seizures: a video-EEG monitoring study.

The authors conducted a randomized trial of second-line anticonvulsant treatments for neonates. The response to treatment was assessed using continuous video-EEG because the clinical diagnosis of seizure in neonates is known to be unreliable. Of 27 neonates with EEG-confirmed seizures, 5 were excluded because of protocol violations, and 11 responded to phenobarbitone in a dose of 40 mg/kg as first line. Three of five neonates treated with lignocaine responded. Six neonates were treated with benzodiazepines as second line: None responded, and their neurodevelopmental outcome was poor.

Outcome of electroclinical, electrographic, and clinical seizures in the newborn infant.

Three seizure types have been described in the neonate: electroclinical, electrographic, and clinical only. Controversy still exists about whether the episodic abnormal movements seen in some infants, which are not accompanied by simultaneous ictal discharges on the EEG, are true seizures. Twenty-four infants with seizures were studied, 17 had purely electrographic and/or electroclinical seizures, seven had clinical-only seizures; six of these seven had clonic seizures, without facial manifestations or autonomic change. The three seizure types were investigated using video-EEG and a Griffiths neurodevelopmental assessment was performed in each seizure group. Of the seven infants with clinical-only seizures, six had clonic seizures with a normal background EEG, neuroimaging studies and neurodevelopmental follow-up assessment were normal in five. In the remaining 17 infants with electrographic and/or electroclinical seizures, seizure discharges were often associated with ocular phenomena, apnoea, or tonic posturing, and the background EEG was abnormal in all but one subject. Neurodevelopmental follow-up assessments revealed a poor outcome (14 of 17) in this group. In otherwise healthy infants, purely clonic seizures involving only the limbs may be a benign phenomenon and an EEG should be obtained to avoid unnecessary treatment. Infants with seizures superimposed on an abnormal background EEG pattern had a poor outcome.