Seizure-related injuries in a group of young people with epilepsy wearing protective helmets: incidence, types and circumstances.

PURPOSE: To provide information on the incidence, types and circumstances of injuries sustained in a group of young people with epilepsy using protective helmets. METHODS: Thirty-three residential students (21 M, 12 F, age range 5-21, mean 14.5 years) attending a special epilepsy centre over 1 year were provided with helmets. The types of protective measures, seizure frequency, types of injuries, circumstances and outcome were recorded. RESULTS: Fourteen thousand seven hundred and fifty-one seizures were recorded in the 33 patients, which resulted in 59 injuries. The seizure-related injury risk was 4/1000 seizures. Scalp and facial bruises were the commonest injury (51%). Additional protective measures, such as bed guards and padding of dinner tables and sinks, were used for 57% of these students. Helmets were in use in 46% of the accidents; 68% of these accidents resulted in facial or scalp injuries, which required medical attention in 48%. Helmets were not in use in 41% of accidents; 57% of these accidents resulted in facial or scalp injuries, which required medical attention in 36%. Data on wearing of helmets in the accidents were unavailable in 13%. CONCLUSIONS: Injuries continue to occur despite the use of helmets. Changes to the helmet design and modifications to suit the seizure type may improve the protection offered by helmets.

Is generic prescribing acceptable in epilepsy?

There is considerable debate about the role of generic prescribing for people with epilepsy. The arguments go beyond simple considerations of cost on one hand and the possibility of toxicity or loss of seizure control on the other. The concepts of bioavailability and bioequivalence require further consideration. The measures that are currently used may not apply equally well to all situations. For example, additional measures may be needed for controlled-release preparations and in the other special cases. There is an extensive literature on the bioequivalence of various phenytoin preparations. This anticonvulsant drug is poorly soluble in water, has nonlinear kinetics and has a narrow therapeutic range, implying that problems with bioequivalence are likely to occur. This is borne out by clinical experience. There are a few published investigations on carbamazepine. The systematic studies, on the whole, fail to show major differences in bioequivalence between the various formulations. There is sparse information on the comparison between generic and proprietary formulations of other anticonvulsant drugs. Whatever arguments might be put forward supporting brand name or generic prescribing, there are strong reasons for recommending tight control on the consistency of anticonvulsant drugs, both generic and proprietary. There is also a strong case for ensuring that the physician who signs the prescription remains in control of the situation and that any decisions that the physician makes should be based on accurate and reliable information.

Behavioural effects of the new anticonvulsants.

Of the 9 new anticonvulsants that have been marketed recently in the UK or US, a number appear to have either adverse or beneficial effects on behaviour. There is now a considerable database of information, in terms of the number of patients treated and/or the number of published reports, on vigabatrin, lamotrigine, gabapentin and topiramate. Oxcarbazepine has been available in some centres for several years and there is extensive experience with the drug in Scandinavia. It appears that the profile of adverse and beneficial effects is similar to that of carbamazepine. Behavioural effects have probably been greatest with vigabatrin, with psychosis, depression and other behavioural problems recorded, but the use of this drug has been limited because of the concern about visual field constriction. The cognitive and behavioural effects of topiramate have caused concern, but these may be much less of a problem if lower starting dosages and escalation rates are used. Psychosis and depression have been associated with topiramate, as they have with another carbonic anhydrase inhibiting drug, zonisamide. Although zonisamide has been used for many years in Japan and Korea, experience elsewhere with this drug is currently very limited. Gabapentin seems to be less associated with adverse behavioural effects than some of the other new anticonvulsant drugs. The reports of behavioural disturbance with gabapentin in children may be related to dose escalation. Behavioural disturbance as a direct result of lamotrigine seems to be uncommon, although indirect effects on behaviour, through the so-called 'release phenomenon' from improved seizure control and consequent ability to misbehave, can occur. Positive behavioural effects have been described with several of the new anticonvulsants, particularly gabapentin, lamotrigine and oxcarbazepine; all of these drugs may have mood-levelling effects that could be of value in treating affective disorders. The information on tiagabine and levetiracetam is too limited to allow any firm conclusions to be drawn with regard to positive or negative behavioural effects. When interpreting reports of behavioural changes with anticonvulsants, it is important to avoid attributing the effect to the drug when one or more of the other multiple causes of behavioural disturbance in people with epilepsy may be responsible or when an indirect effect such as 'forced normalisation' may be the cause. Many of the published studies are retrospective and unblinded rather than double-blind, placebo-controlled, prospective trials, implying that much of the data must be interpreted with caution at this stage.

The therapeutic dilemma: treating subtle seizures or indulging in electroencephalogram cosmetics?

The treatment of epileptiform abnormalities in the absence of obvious seizures has, in the past, been dismissed as "EEG cosmetics." The work on transitory cognitive impairment has highlighted the importance of asking the question: "What is a seizure?" The extent to which epileptiform discharges cause temporary or permanent impairment, profoundly influences decisions on whether to treat with antiepileptic medication or surgery.

Safety, tolerability, and pharmacokinetics of remacemide in children.

Eleven patients (nine males, two females), 9-14 years of age, received adjunctive therapy with remacemide in an open ascending-dose study at two residential centers in the United Kingdom. Children taking enzyme-inducing drugs were given remacemide twice daily, starting at approximately 4 mg/kg per day and doubling the dose at two weekly intervals to a target dose of approximately 16 mg/kg per day. Children not taking enzyme-inducing drugs (n = 5) received half of these doses. After the dose-escalation phase, remacemide was slowly withdrawn over 2 weeks except in two children who, because of apparent benefit, entered a continuation phase. Remacemide generally was well tolerated in doses up to 13.5 mg/kg per day. Adverse events were similar to those reported in adults, with central nervous system and gastrointestinal events being the most common. One patient died after a suspected seizure, which was unlikely to have been related to remacemide treatment. No adverse effects on neuropsychologic functioning were observed; effects on vital signs and laboratory variables were not clinically significant. The pharmacokinetic profile for remacemide and its desglycinyl metabolite in children is similar to that seen in adult patients. Plasma concentrations of remacemide and the desglycinyl metabolite are reduced in the presence of concomitant antiepileptic drugs with hepatic enzyme-inducing activity.

Lamotrigine--managing the challenging patient.

Childhood epilepsy presents many different challenges requiring a careful assessment and an individual management plan appropriate to the needs of each child. The first rule in managing the difficult-to-treat patient is to re-examine the diagnosis. The characterization of the seizures may also guide the clinician into prescribing the appropriate therapy. If the child has failed to respond to first-line antiepileptic drugs, the situation should be reviewed carefully. There may be a role for one of the new antiepileptic drugs. It is important to treat with adequate doses and for adequate duration before deciding whether a drug is effective or not. Failure to do this may deny the child the benefit of a particular medication. Drugs which affect behaviour or cause lethargy can have a secondary effect on cognition. Failure to treat frequent subtle seizures may also have serious cognitive consequences. Lamotrigine is of value in treating a variety of different seizure types, including subtle seizures, and has a low incidence of adverse effects.

Successful re-introduction of lamotrigine after initial rash.

The aim of this study was to determine whether lamotrigine can be re-introduced safely and with a benefit in young people who previously had a mild rash associated with the first introduction of this drug. In the first 150 young people (5-19 years old) treated with lamotrigine in a special centre for epilepsy, seven developed a mild rash soon after starting the drug. In none of these cases was the rash severe, nor was there any mucous membrane involvement. The lamotrigine was stopped immediately when the rash was identified and was subsequently re-introduced, using a special very-low-dose-escalation regime, starting with 0.1 mg /day total daily dose, after periods ranging from 47 to 236 days. It was possible to re-introduce the lamotrigine without recurrence of persistent rash and without any adverse effects in all seven cases. The re-introduction of lamotrigine was associated with improvement in five of the seven cases. It is recommended that lamotrigine is stopped as soon as any rash attributable to the drug develops but it may be possible to re-introduce the drug after mild rash using a very-slow-dose-escalation regime, with a benefit in at least some cases.

An audit of children referred with suspected epilepsy.

Members of the British Paediatric Neurology Association were invited to participate in a national audit of children presenting with a possible diagnosis of epilepsy. The audit was based on a 'standard' or set of pre-determined questions drawn up by an advisory audit group. The audit form comprised a total of 30 questions divided into four sections addressing history, examination, investigation, treatment and communication. Information for the audit was obtained retrospectively from the child's case notes. Each participating centre or consultant was asked to audit the case notes of 20 children. At the end of the 12-month recruitment period three centres responded, contributing audit forms on 50 children. The required information was provided for the majority of the questions in each of the four sections, thereby meeting the audit 'standard'. Within the history section, only 32 of the 50 (64%) case notes had recorded whether or not there was 'any obvious provoking factor or circumstance to the episodes'. Communication was the least satisfactorily completed section with between none and 48% of the case notes documenting that the child's family had been informed of the existence of a voluntary epilepsy organization. Despite the simplicity of the audit form, the response for this national audit was considerably lower than anticipated.

Long-term safety and efficacy of lamotrigine (Lamictal) in paediatric patients with epilepsy.

This study was initiated to evaluate the long-term safety, tolerability and effect on seizure control of lamotrigine (Lamictal) in paediatric patients with epilepsy. A total of 155 children (aged 2-19 years) with treatment-resistant epilepsy received add-on therapy or monotherapy lamotrigine for up to four years. Patients had already experienced benefit from lamotrigine treatment in an open one-year study before entering this open continuation study of up to three additional years of treatment. Overall, including both these studies, patients were treated with lamotrigine for 53-221 weeks, representing 417.9 patient-years of experience. The physician's global assessment of seizure control compared to the three-month period before lamotrigine treatment, indicated that seizure control was generally maintained during long-term lamotrigine treatment for up to four years. For 19 patients, the investigator recorded a subjective improvement in behaviour, alertness, seizure severity, quality of life and mobility with lamotrigine treatment, sometimes independent of seizure control. In total, 34 patients received lamotrigine monotherapy; 22 of these were maintained on lamotrigine monotherapy for at least one year. Lamotrigine was well tolerated. The majority of adverse experiences were classified by the physician as being mild in intensity and only six patients (4%) withdrew from the study due to adverse experiences.

Treatment of photosensitive epilepsy using coloured glasses.

A recently introduced optometric technique, colorimetry, enables the perceptual effects of ophthalmic tints to be evaluated subjectively, optimized, and then prescribed in tinted spectacles. The new technique is beneficial in reducing visual stress in patients with dyslexia and migraine. We describe an open trial designed to ascertain: (1) whether the colorimetry assessment, as it is now given, is safe for the investigation of photosensitive patients in optometry clinics where colorimetry equipment is most readily available, but where EEG control is not practical; (2) what proportion of patients with photosensitive epilepsy is likely to benefit to the extent already described in individual cases; (3) whether a tint selected by colorimetry could be shown to reduce the incidence of paroxysmal epileptiform EEG activity in response to flicker and patterns, thereby validating the subjective methods and corroborating the reported seizure reduction. Twenty-four females and nine males (aged 12-43 years) took part. All the patients had suffered visually-provoked seizures, had exhibited a photoparoxysmal response on at least one previous EEG recording, and had received a diagnosis of photosensitive epilepsy. Twenty-two were currently experiencing seizures. A further EEG was recorded in all except seven cases: a routine resting record, followed by hyperventilation. Colorimetry was performed after hyperventilation and before photic stimulation. Twenty-three (70%) reported beneficial effects during colorimetry and were prescribed glasses. There was a preponderance of lenses with a rose or purple colour, in contrast to patients with dyslexia. Seventeen of the 23 patients were available at follow-up, an average of 2.4 years later. Thirteen (57%) reported benefits, and said they were still using the lenses. In six of the 13 the benefits were pronounced, including a reduction of dizziness from fluorescent lighting, elimination of aura when using computer screens etc. Only in three cases was there a reduction in seizures that could reasonably be attributed to the use of lenses; in two of these cases no medications were prescribed, and in the third the medications remained unchanged for four years, two before and two after the introduction of the glasses. In an additional four cases a reduction in seizures was observed but medication had been changed. There was a modest reduction in EEG photosensitivity with the coloured lenses but also to an equivalent or lesser extent with grey in all of the eight patients examined in this way. One patient had seizures during colorimetry, but the seizures were not accompanied by scalp EEG changes.

Changing trends in antiepileptic drug prescribing in girls of child-bearing potential.

OBJECTIVE: To characterize trends in prescribing carbamazepine (CBZ), sodium valproate (VPA) and lamotrigine (LTG) in adolescent females in the UK and to examine possible reasons for changing trends. DESIGN: Population-based observational study. SETTING: UK General Practice Research Database between 1 January 1993 and 31 December 2006. PATIENTS: 12-18-year-old subjects who were issued >or=1 CBZ, VPA or LTG prescription. MAIN OUTCOME MEASURES: Prescribing prevalences stratified by age, gender and antiepileptic drug. RESULTS: 5417 patients (47.6% females) were prescribed 147 111 prescriptions for CBZ (34.5%), VPA (38.6%) or LTG (26.9%). The prevalence of LTG prescribing in females increased from 0.08 (95% CI 0.04 to 0.12) to 0.80 (95% CI 0.70 to 0.89) per 1000 female population. Conversely, the prevalence in females of CBZ and VPA prescribing significantly decreased from 1.00 (95% CI 0.85 to 1.15) to 0.51 (95% CI 0.44 to 0.58) and from 0.94 (95% CI 0.80 to 1.09) to 0.63 (95% CI 0.55 to 0.72), respectively. This 10-fold rise in LTG prescribing in females is much higher than the fivefold rise in males from 0.09 (95% CI 0.05 to 0.14) to 0.47 (95% CI 0.40 to 0.54) per 1000 male population. CONCLUSION: The practice of prescribing antiepileptic drugs in adolescents has changed gradually over the last decade. More females aged 12-18 years are prescribed LTG than CBZ or VPA and the increase is much greater than for males. The increase in LTG prescribing mirrors a corresponding decrease in both VPA and CBZ. Concerns about potential problems to offspring appear to be affecting prescription trends in adolescent females of child-bearing potential.

Lamotrigine in the treatment of epilepsy in people with intellectual disability.

Information about the mechanism of action and pharmacology of lamotrigine is summarized. A brief review of the literature on the use of this drug in people with intellectual disability is followed by a suggested framework for evaluating antiepileptic drugs in this population. The role of lamotrigine is systematically examined against the suggested framework. This leads to the conclusion that lamotrigine is a very favourable drug for treating epilepsy in people with intellectual disability because it has a broad spectrum of action, is effective in treating subtle seizures, shows no loss of effect with time, is not usually sedative, does not produce difficult-to-manage adverse effects, appears to have no direct adverse behavioural effects and is available in a range of 'patient friendly' preparations. However, it is important to use the drug wisely. This implies starting with low doses of lamotrigine and escalating the dose slowly to avoid adverse effects, especially rash, and being aware of drug interactions which could cause difficulty, including the prolongation of half-life with valproate, the pharmacodynamic interaction when it is added to carbamazepine and the pharmacokinetic interactions of lamotrigine with a number of antiepileptic drugs.

Modern management of epilepsy: Adolescents.

Epilepsy most commonly starts in the first two decades of life. Adolescence is a time of great change both in the epilepsy itself and in a number of other areas. Growth into adulthood, issues of preparation for university or employment, driving, drinking, preparation for marriage/conception and a general increase of responsibility add to the complexity of this time of life. Epilepsy affects all these areas to a significant degree. The incidence of several epilepsy syndromes peaks in adolescence. These include juvenile myoclonic epilepsy, juvenile absence epilepsy, epilepsy with grand mal on awakening, benign partial seizures of adolescence and reading epilepsy. Photosensitivity also appears to peak around puberty and needs to be managed well to avoid both unreasonable risks and unnecessary restrictions. Early diagnosis and correct management of the epilepsy and the specific epilepsy syndrome are the main factors in minimizing the difficulties. Epilepsy may change in the early adolescent years, with seizures starting and stopping or altering in form, all of which add to the uncertainty. Denial of the epilepsy may lead to risk-taking which may include be provided on the high risk of the unsupervised bath, the effect of irregular sleep, alcohol, driving, sport, employment, genetic implications, advantages/adverse effects of specific antiepileptic drugs and the role of surgery. The doctor should listen, counsel and inform. Adolescents generally do not appreciate being given advice. They should be empowered by the doctor to make informed decisions and encouraged to take control in a situation which they may view as implying devastating loss of control, unless it is managed wisely.

Epilepsy, learning, and behavior in childhood.

Several major issues exist with regard to epilepsy and learning in childhood. A small subgroup of children have a decreasing I.Q. In addition, a high proportion of children with epilepsy, possibly one half, have some schooling difficulties. Learning problems may be a consequence of the epilepsy or a result of associated factors. It is important to distinguish between the slowing of acquisition of skills and actual loss of skills; the practical implications for the child and family are very different in these two situations. In the very small proportion of children in whom actual loss of skills occurs, it is essential to seek a cause, because a cause can usually be identified and may require specific management. The importance of distinguishing between state-dependent, potentially reversible intellectual impairment and permanent impairment cannot be overemphasized. State-dependent intellectual impairment, e.g., arising from ongoing nonconvulsive status epilepticus (NCSE) or antiepileptic drug (AED) toxicity, must be identified and every effort made to eliminate it. Studies at St Piers Lingfield have shed light on these issues although the answers to many of the questions remain incomplete. Educational difficulty is among the factors that may affect behavior. However, there are many other causes for behavioral disturbance in the child with epilepsy. A specific framework for assessing the child with epilepsy and behavioral disturbance allows the cause or causes of the behavioral disturbance to be identified and managed in a rational way.

Use of antiepileptic drugs in the treatment of epilepsy in people with intellectual disability.

The main principles of antiepileptic drug treatment of epilepsy in patients with intellectual disability are basically the same as for other patients with epilepsy. However, some specific issues need to be taken into account These are primarily associated with the diagnostic difficulties of epilepsy in this population. In addition, a number of other relevant issues, including the degree and location of brain lesion, the nature of the underlying disease, the higher frequency of difficult-to-treat epilepsies, the additional intellectual impairment caused by inappropriate antiepileptic medication, or by frequent and prolonged seizures, the appropriate use of monotherapy versus rational polytherapy, and the use of broad-spectrum antiepileptic drugs will be discussed in the present paper. Although the goals of treatment are to keep the patient seizure-free and alert while preventing possible mental deterioration, we have to accept compromises between these primary goals in many cases. Some people with epilepsy and intellectual disability are very vulnerable to insidious neurotoxic effects; for example, sedative effects caused by phenobarbital, or cognitive and/or cerebellar dysfunction caused by long-term phenytoin, especially together with other drugs. Because of the adverse effects of phenobarbital and phenytoin, these drugs are no longer recommended as a first-choice drugs when long-term antiepileptic medication is required. In primary generalized tonic-clonic seizures, valproate, oxcarbazepine/carbamazepine and lamotrigine are recommended in this order of preference. The corresponding recommendations are: in typical absences, valproate, ethosuximide and lamotrigine; in atypical absences, valproate and lamotrigine; in juvenile myoclonic epilepsy, valproate, lamotrigine and clobazam; in infantile spasms vigabatrin, ACTH and valproate; in Lennox-Gastaut syndrome, valproate, lamotrigine and vigabatrin; in atonic seizures, valproate and lamotrigine; in simple and complex partial seizures with or without secondary generalization, oxcarbazepine/carbamazepine, valproate/ vigabatrin and lamotrigine; and in status epilepticus lorazepam, diazepam and clonazepam together with phenytoin or fosphenytoin. In cases of poor response to the monotherapy recommended above, the following combinations may be indicated: in primary generalized tonic-clonic epilepsy, valproate and oxcarbazepine/ carbamazepine, or valproate and lamotrigine; in typical absences, valproate and lamotrigine, or valproate and ethosuximide; in juvenile myolonic epilepsy, valproate and lamotrigine, or valproate and clonazepam; and in partial epilepsies, add to the monotherapy one of the following drugs, vigabatrin, lamotrigine, gabapentin, tiagabine, topiramate, zonisamide or clobazam. So far, the order of preference of these new drugs remains undetermined. More data are needed on the efficacy and adverse effects of the new drugs based on controlled studies on patients with intellectual disability and epilepsy.

Methsuximide lowers lamotrigine blood levels: A pharmacokinetic antiepileptic drug interaction.

PURPOSE: To determine whether methsuximide (MSM) affects lamotrigine (LTG) blood levels and whether any change is of clinical significance. METHODS: LTG serum levels in 16 patients taking MSM were compared with those before starting or after stopping the MSM. The 16 patients, (11 boys, five girls) were young people (mean age, 15.5 years; range, 9-19 years) with a variety of seizure types and syndromes. In six cases, LTG levels were available both before MSM was started and after it was stopped. RESULTS: The mean LTG serum concentration before starting or after stopping MSM was 13.4 mg/L, and the mean level while taking MSM was 6.3 mg/L. This difference was highly significant (p < 0.0005, paired t test). MSM lowered the LTG serum concentration in every case, with a mean decrease of 53% (range, 36-72%). In some patients this led to a deterioration in seizure control when MSM was added or an improvement in seizure control after MSM was stopped. CONCLUSIONS: Although MSM is a valuable add-on, broad-spectrum drug when used in combination with LTG, adjustment of the LTG dose may be necessary when MSM is started or stopped, to allow for the fact that MSM lowers LTG blood levels.

Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomised trial.

BACKGROUND: Convulsive status epilepticus is the most common neurological medical emergency and has high morbidity and mortality. Early treatment before admission to hospital is best with an effective medication that can be administered safely. We aimed to find out whether there are differences in efficacy and adverse events between buccal administration of liquid midazolam and rectal administration of liquid diazepam in the acute treatment of seizures. METHODS: At a residential school with on-site medical facilities 42 young people with severe epilepsy were enrolled. Continuous seizures of more than 5 min duration were randomly treated with buccal midazolam or rectal diazepam. If the seizure did not stop within 10 min additional medication chosen by the attending physician was administered. We monitored oxygen saturation and blood pressure for 30 min after treatment. The main outcome measures were efficacy, time from arrival of the nurse to drug administration, time from drug administration to end of seizure, and incidence of adverse cardiorespiratory events. FINDINGS: Buccal midazolam was used to treat 40 seizures in 14 students, and rectal diazepam 39 seizures in 14 students. Midazolam stopped 30 (75%) of 40 seizures and diazepam 23 (59%) of 39 (p=0.16). The median time from arrival of the nurse to administration of medication was 2 min. Time from administration to end of seizure did not differ significantly between the two treatments. No clinically important adverse cardiorespiratory events were identified in the two groups. Buccal midazolam was universally acceptable to the nursing and care staff. INTERPRETATION: Buccal midazolam is at least as effective as rectal diazepam in the acute treatment of seizures. Administration via the mouth is more socially acceptable and convenient and may become the preferred treatment for long seizures that occur outside hospital.

Effects of transitory cognitive impairment on psychosocial functioning of children with epilepsy: a therapeutic trial.

The authors report a trial of the use of anti-epileptic medication to treat possible cognitive deficits due to subclinical epileptiform EEG discharges in 10 children with psychosocial and educational problems associated with epilepsy. Medication intended to suppress the EEG discharges was added to the children's existing drug regime. In all instances, epileptiform activity, assessed by 24-hour periods of ambulatory monitoring, was reduced on active medication compared with placebo. In general, there was improvement of psychosocial function on active treatment: eight children improved, there was no change in one and one deteriorated. No psychosocial deterioration attributable to adverse effects of the medication was detected in those completing the trial. Despite possible confounding factors, the findings are in accordance with the view that subclinical EEG discharges can impair psychosocial function, which may be ameliorated by anti-epileptic medication.