Prolonged recovery of consciousness in children following symptomatic epileptic seizures.

INTRODUCTION: There is little published data on the duration of depressed consciousness following epileptic seizures. A prolonged recovery time may be a symptom of underlying brain pathology. This prospective paediatric cohort study investigates whether recovery is prolonged following symptomatic seizures. METHODS: Children aged 1-16 years, who had a witnessed seizure in which consciousness was impaired, were recruited. One hundred and twenty eight children (158 seizures) were studied. Seizure aetiology was classified as febrile, idiopathic, remote symptomatic, acute symptomatic and acute on remote symptomatic. At least hourly Paediatric Coma Scale recordings were used to assess recovery time. RESULTS: Recovery time was longest for children with acute on remote symptomatic seizures (4.0 h, range 0.89-10.5), followed by those with acute symptomatic seizures (1.94 h, range 0-35.27), remote symptomatic seizures (1.5h, range 0.07-85.5) and idiopathic seizures (0.83 h, range 0.07-13.13). Children with febrile seizures recovered the quickest (0.3h, range 0.05-9). Recovery time was significantly longer (p<0.001, CI 1.96-5.38) following seizures for which rescue antiepileptic drugs were administered compared to those for which it was not. Age, sex, type and duration of seizure did not independently affect recovery time. DISCUSSION: Symptomatic seizures take longer to recover than seizures of other aetiologies. It is recommended that a febrile child who presents with a seizure, who has not fully recovered within 30 min, should be investigated for an acute symptomatic aetiology. A high index of suspicion is also needed if children with apparent idiopathic seizures have not fully recovered within 1.5h.

Corticosteroids including ACTH for childhood epilepsy other than epileptic spasms.

BACKGROUND: Epilepsy is a disorder with recurrent epileptic seizures. Corticosteroids have been used in the treatment of children with epilepsy and have significant adverse effects. Their efficacy and tolerability have not been not clearly established. OBJECTIVES: To determine the efficacy of corticosteroids in terms of seizure control, improvements in cognition and in quality of life and tolerability of steroids compared to placebo or other antiepileptic drugs. SEARCH STRATEGY: We searched the following databases: The Cochrane Epilepsy Group Specialized Register (September 2006); Cochrane Central Register of Controlled Trials (CENTRAL)(The Cochrane Library Issue 2, 2006); MEDLINE (1966 - April 2004); EMBASE (1966 - December 2004); Database of Abstracts of Reviews of Effectiveness (DARE) (December 2004). We checked the reference lists of retrieved studies for additional reports of relevant studies. SELECTION CRITERIA: All randomized controlled trials of administration of corticosteroids to children (less than 16 years) with epilepsy. DATA COLLECTION AND ANALYSIS: Three review authors independently selected trials for inclusion and extracted data. Outcomes included cessation of seizures, reduction in seizure frequency, improvement in cognition, quality of life and adverse effects of steroids. MAIN RESULTS: A single RCT was included that recruited five patients in double blind crossover trial. One was withdrawn prematurely from the study and another had infantile spasms and hence was excluded from further analysis. ACTH 4-9 was administered. The overall reduction in seizure frequency of more than 25% and less than 50% occurred in one child at low dose and in two children at higher dose. One child did not show any reduction in seizure frequency. No adverse effects were reported. AUTHORS' CONCLUSIONS: No evidence was found for the efficacy or safety of corticosteroids in treating childhood epilepsies. Clinicians using steroids in childhood epilepsies, other than for epileptic spasms, should take this into account before using these agents.

Posterior agyria-pachygyria with polymicrogyria: evidence for an inherited neuronal migration disorder.

We describe two brothers with mental retardation and refractory epilepsy. MRI revealed symmetrical agyria-pachygyria of the temporo-occipito-parietal regions, areas of deeply infolded polymicrogyric parietal cortex, and dilated occipital horns (colpocephaly). The stereotyped clinical, EEG, and MRI findings suggest that this may be a distinct inherited condition and imply that agyria-pachygyria with polymicrogyria is not always sporadic.

Vagal nerve stimulation in epileptic encephalopathies.

OBJECTIVE: To study the effect of vagal nerve stimulation (VNS) in children with epileptic encephalopathies. METHODS AND MATERIALS: All children receiving VNS during a 2-year period at our center were studied prospectively for changes in seizure frequency, electroencephalogram (EEG), adaptive behavior, quality of life, and where appropriate, verbal/nonverbal performance. Assessments were made before and for at least 1 year after implant. RESULTS: Sixteen children were studied. One device was removed because of infection. Of the remaining 15 children, 4 had a >50% reduction and 2 had a >50% increase in seizure frequency at 1 year after implant. Median reduction in seizure frequency was 17%. There was no trend toward improvement of the EEG or adaptive behavior. Quality of life was unchanged in most areas, except in perceived treatment side effects and general behavior that were improved. In 6 children undergoing further assessment, there was a significant improvement in verbal performance; this did not correlate with reduction in seizure frequency. CONCLUSION: VNS did not significantly improve seizure frequency, severity, adaptive behavior, or the EEG during the first year of treatment for the group as a whole, although 4 children (27%) had a worthwhile reduction in seizure frequency. There were significant improvements in perceived treatment side effects and general behavior.

Visual and semiquantitative analysis of cortical FDG-PET scans in childhood epileptic encephalopathies.

UNLABELLED: The optimal method for analyzing PET scans in children being considered for epilepsy surgery is unresolved: Fully quantified methods are invasive, and the required controls are generally unavailable. We sought to compare visual inspection with semiquantitative analysis for the detection of cortical metabolic defects. METHODS: Thirty-two children with cryptogenic epileptic encephalopathies were studied prospectively with 18F-fluorodeoxyglucose (FDG) PET. Visual inspection was performed on separate occasions by independent observers. Four-millimeter circular regions of interest were used to sample radiotracer uptake in selected cortical regions. Asymmetry between homologous regions were calculated to detect focal abnormalities. Bilateral and diffuse abnormalities were assessed by comparing the ratio of cortical-to-cerebellar uptake in patients with historical age-matched controls. The sensitivity and specificity of visual inspection was compared with that of semiquantitative analysis for the detection of focal, bilateral and diffuse cortical metabolic abnormalities. RESULTS: Visual inspection revealed full inter-rater agreement for the presence of major focal abnormalities. The sensitivity and specificity for visual inspection compared to semiquantitative analysis were 77% and 92%, respectively, with semiquantitative analysis often revealing abnormalities to be more extensive than had been suspected visually. Compared with semiquantitative analysis, visual inspection had a low sensitivity but high specificity for the detection of bilateral and diffuse hypometabolism. CONCLUSION: Semiquantitative analysis gives clinically useful information additional to that obtained from visual inspection.

Plasma amino acids in childhood epileptic encephalopathies.

Abnormalities in plasma amino acid levels have been noted in patients with various epilepsies, and sometimes also in their first degree relatives. We sought to study plasma amino acid levels in children with epileptic encephalopathies and their parents, relating findings to the pattern of cortical glucose metabolism as determined by 18fluorodeoxyglucose (FDG) positron emission tomography (PET). Twenty-eight children with cryptogenic epileptic encephalopathies were studied prospectively. Cortical glucose metabolism was evaluated by FDG PET with combined visual and semiquantitative analysis used to detect focal cortical defects. The plasma concentration of 21 amino acids in the children and their parents was measured by ion exchange chromatography and compared with control values using non-parametric statistical methods. Multivariate analysis was used to assess antiepileptic drug effects. Children were classified as: Lennox-Gastaut syndrome following infantile spasms (six patients); de-novo Lennox-Gastaut syndrome (eight); severe myoclonic epilepsy in infancy (eight) and myoclonic-astatic epilepsy (two). Four patients remained unclassified. Fourteen patients had focal/multifocal abnormalities on PET scans. The plasma level of aspartate was significantly lower in both the children with epileptic encephalopathies and in their parents (P < 0.005). The lowered aspartate levels could not be accounted for by the antiepileptic drug medication taken by the children. Further analysis showed the lowered aspartate levels to be confined to children and their parents who lacked focal PET abnormalities. These findings suggest a possible genetic abnormality in the aspartate neurotransmitter systems in the pathogenesis of seizures in the childhood epileptic encephalopathies.

Topiramate for drug-resistant epilepsies.

Topiramate is a new anti-epileptic drug with proven efficacy against partial seizures in adults. A retrospective assessment of the use of topiramate in drug-resistant childhood epilepsy was undertaken. Thirty-four children (median age of 10 years; range 2-18 years) were treated for a median of 9 months (range 6-18 months). The starting dose was 0.25-2.0 mg/kg/day increasing to a maximum of 13 mg/kg/day. Generalized seizures occurred in 27 patients, partial seizures in 15 and infantile spasms in two. Epilepsies were localization-related in 15 patients and generalized in 18. One patient had severe myoclonic epilepsy in infancy. Two patients had Lennox-Gastaut syndrome, five (two currently and three previously) had West syndrome and one had epilepsy with myoclonic absences. Twenty patients had a substantial (> 50%) reduction in seizure frequency; two of whom became seizure-free. Two-patients had an increase in seizures. Efficacy was seen against simple and complex partial seizures, generalized tonic-clonic seizures (primarily generalized), atonic and tonic seizures, myoclonic seizures and infantile spasms. There was no response in the one patient with myoclonic absence seizures. Adverse effects were reported in nine patients; appetite suppression occurred in five patients, behaviour disturbances in three, somnolence in two and poor concentration in one patient. Topiramate is efficacious in a wide spectrum of childhood epilepsies and is well tolerated.

Qualitative and quantitative abnormalities of breath counting during brief generalized 3 Hz spike and slow wave 'subclinical' discharges.

We aimed to validate the technique of breath counting during overbreathing in revealing ictal impairment of cognition during brief generalized 3 Hz spike and slow wave discharges. A retrospective study of 66 patients with video-electroencephalographic documentation of typical absence seizures revealed 8 patients in whom there was no clinical suspicion of absences but who had brief (less than 4 seconds) generalized 3 Hz spike-wave discharges. The only clinical manifestations of the absences were abnormalities in breath counting during overbreathing. These consisted of slowing of speech, delay in counting, repetition of numbers and counting out of sequence combined with delay. Abnormalities were more likely to occur during longer discharges. Detection of these abnormalities led to important changes in the classification of the patients' epilepsies and in the recommendations for treatment. The technique of breath counting during overbreathing is a simple practical and reliable method for detecting even mild cognitive impairment during 3 Hz spike-wave discharges.

Therapeutic interaction of lamotrigine and sodium valproate in intractable myoclonic epilepsy.

The clinical and EEG features of a 13-year-old girl with an unusual refractory myoclonic epilepsy is presented. Control was achieved only when lamotrigine was combined with sodium valproate. This may represent a specific pharmacodynamic interaction between these drugs with implications for therapy in the generalized epilepsies.

Idiopathic generalised epilepsy with phantom absences and absence status in a child.

A syndrome of idiopathic generalised epilepsy with phantom absences of undetermined onset has been recently described. This syndrome clinically becomes apparent in adulthood with generalised tonic clonic seizures and frequently absence status epilepticus. We report an 11 year-old normal girl with frequent episodes of absence status and no other overt clinical manifestations. However, appropriate video-EEG recordings documented that she had frequent absence seizures that were so mild as to escape recognition by her and the parents. These consisted of mild impairment of cognition and eyelid fluttering during brief generalised discharges of spike/multiple spike and slow waves. No further seizures occurred and the EEG normalised after appropriate drug treatment. Thus, it appears that this syndrome of phantom absences and absence status may start much earlier, in late childhood. Appropriate video-EEG documentation is needed for the recognition of these patients that may be more common than it appears from the few published cases (with Video).

Recovery of consciousness after epileptic seizures in children.

OBJECTIVE: To investigate the duration of postictal impairment of consciousness and the factors that affect it. PATIENTS AND METHODS: 90 children aged 1-16 years (37 male, 53 female, median age 6 years), attending the accident and emergency department, and inpatients of Leeds General Infirmary, Leeds, UK, who had experienced seizures involving impairment of consciousness. Interventions-hourly modified paediatric coma scores were determined, until a coma score of 15 was obtained. Linear regression analysis was used to determine the factors influencing recovery time. RESULTS: 49 children were excluded owing to incomplete coma scoring, lost notes and refusal of consent. Median time for full recovery of consciousness was 38 min (0.63 h, range 0.05-17 h). Median recovery time was 18 min (0.3 h, range 0.05-9 h) from febrile seizures, which was significantly shorter than for seizures of other aetiologies (p<0.05), 1.35 h (range 0.07-13.13 h) from idiopathic seizures, 1.25 h (0.07-12.1 h) from remote symptomatic seizures and 4.57 h (0.25-17 h) from acute symptomatic seizures. Median recovery time after the use of benzodiazepines was 3.46 h (range 0.08-14.25 h), and was significantly longer (p<0.05) than for seizures not treated with benzodiazepines (median 0.47 h, range 0.05-17 h). Age, sex, seizure type and duration did not significantly affect recovery time. CONCLUSIONS: Most children experiencing febrile seizures recover within 30 min. An acute symptomatic aetiology should be considered if recovery takes >1 h.

Paroxysmal extreme pain disorder (previously familial rectal pain syndrome).

OBJECTIVE: To describe the clinical phenotype of paroxysmal extreme pain disorder (previously called familial rectal pain syndrome), an autosomal dominant condition recently shown to be a sodium channelopathy involving SCN9A. METHODS: An international consortium of clinicians, scientists, and affected families was formed. Clinical details of all accessible families worldwide were collected, including age at onset, features of attacks, problems between attacks, investigational results, treatments tried, and evolution over time. A validated pain questionnaire was completed by 14 affected individuals. RESULTS: Seventy-seven individuals from 15 families were identified. The onset of the disorder is in the neonatal period or infancy and persists throughout life. Autonomic manifestations predominate initially, with skin flushing in all and harlequin color change and tonic attacks in most. Dramatic syncopes with bradycardia and sometimes asystole are common. Later, the disorder is characterized by attacks of excruciating deep burning pain often in the rectal, ocular, or jaw areas, but also diffuse. Attacks are triggered by factors such as defecation, cold wind, eating, and emotion. Carbamazepine is effective in almost all who try it, but the response is often incomplete. CONCLUSIONS: Paroxysmal extreme pain disorder is a highly distinctive sodium channelopathy with incompletely carbamazepine-sensitive bouts of pain and sympathetic nervous system dysfunction. It is most likely to be misdiagnosed as epilepsy and, particularly in infancy, as hyperekplexia and reflex anoxic seizures.

Two siblings with a new Aicardi-Goutières-like syndrome.

We present two siblings (male and female) with very similar characteristics comprising dysmorphic features, severe developmental delay, progressive microcephaly, tonic seizures, and hypothyroidism. The male also had micropenis and cryptorchidism. Both children developed pericardial effusions which caused the death of the female at age 16 months. The male's cardiac function was stable at last follow-up at the age of 15 months. Cerebral imaging showed widespread intracranial calcifications, delay in myelination, hypoplasia of the corpus callosum, and cerebral atrophy. CSF examination showed normal CSF white-cell count and was negative for interferon, although a cytotoxic antibody was thought to be present. Other causes of a neurodegenerative condition and congenital infection were excluded. The combination of these features has not been described before. We believe that these patients represent a new syndrome which has some of the features of Aicardi-Goutières syndrome but is distinct from it.

Psychotic and severe behavioural reactions with vigabatrin: a review.

Behavioural disturbances and psychotic reactions are commoner in patients with epilepsy than in the general population and may be precipitated by the majority of antiepileptic drugs, including the newer ones. These reactions may be more frequent in patients with complex partial seizures, reflecting underlying temporal lobe pathology. A review of the literature on vigabatrin found an incidence of severe abnormal behaviour in controlled trials in adults of 3.4%. In children open studies gave an incidence of around 6%. This may be related to dosage and speed of introduction. Such reactions may be related to changes in seizure control, either unaccustomed good control (force normalisation) or breakdown in control, implying non-specific causative mechanisms. Alternatively, any relationship to control may be fortuitous and specific, unknown pharmacological mechanisms may be involved. Appropriate risk reduction measures include slow introduction, limiting the dose to that required for seizure control, slow withdrawal and increased vigilance in those on polytherapy or with psychiatric histories. Such advice is pertinent to all antiepileptic medications. Additionally, vigabatrin is probably contraindicated in idiopathic generalised epilepsies. Behavioural reactions are uncommon with vigabatrin, and have not been shown to be greater with it than with other antiepileptic agents. Therefore, it maybe inappropriate to withhold the drug from those who may benefit from it.

Neurovascular compression of the trigeminal and glossopharyngeal nerve: three case reports.

Trigeminal neuralgia (TN) is a frequent cause of paroxysmal facial pain and headache in adults. Glossopharyngeal neuralgia (GPN) is less common, but can cause severe episodic pain in the ear and throat. Neurovascular compression of the appropriate cranial nerve as it leaves the brain stem is responsible for the symptoms in many patients, and neurosurgical decompression of the nerve is now a well accepted treatment in adults with both TN and GPN who fail to respond to drug therapy. Neither TN nor GPN are routinely considered in the differential diagnosis when assessing children with paroxysmal facial or head pain, as they are not reported to occur in childhood. Case reports of three children with documented neurovascular compression causing severe neuralgic pain and disability are presented. The fact that these conditions do occur in the paediatric population, albeit rarely, is highlighted, and appropriate investigation and management are discussed.

Cortical and subcortical glucose metabolism in childhood epileptic encephalopathies.

OBJECTIVES: Nearly one third of children with cryptogenic epileptic encephalopathies have been reported to have focal cortical defects on 18fluorodeoxyglucose (FDG) PET. As diffuse cortical dysfunction and involvement of subcortical structures, particularly the thalami, is postulated to underlie the propensity to seizures in these conditions, the aim was to determine the frequency of bilateral and diffuse cortical metabolic defects and of subcortical metabolic abnormalities in the same patients. METHODS: The interictal uptake of FDG was studied in 32 children with epileptic encephalopathies. Using a semiquantitative technique, the ratio of uptake in cortical regions and subcortical structures to that in the cerebellum was compared with that of age matched historical controls. Uptake more than 2 SD above ("hypermetabolic") or below ("hypometabolic") that of age matched controls was considered abnormal. RESULTS: Diffusely abnormal cortical up-take (nearly always hypometabolic) occurred in almost two thirds of patients; in all but two of the remaining patients at least one cortical region showed significantly decreased uptake bilaterally. When analysed as age cohorts, the mean cortical:cerebellar FDG uptake was significantly lower than that of controls in all cortical regions (P<0.005). Ninety per cent of patients had evidence of relative thalamic hypometabolism and in each age group there was a significant reduction in relative thalamic FDG uptake compared with that of controls (P<0.005). In nine out of 11 patients with unilateral cortical hypometabolic defects thalamic FDG up-take was lower ipsilateral to the cortical abnormality. CONCLUSIONS: Diffuse cortical dysfunction is common in the epileptic encephalopathies and may reflect the underlying cause of the condition or arise as a consequence of uncontrolled seizures. Altered thalamic glucose metabolism is further evidence of subcortical involvement in these conditions.