Developmental Medicine and Child Neurology, 32, 567-574. 21. Busto, R., Dietrich, W. D., Globus, M. Y., Valdes, I . , Schejuberg, P., Gunsberg, M. D. (1987) 'Small differences in intraischemic brain temperature critically determine the extent o f ischemic neuronal injury.' Journal of Cerebral Blood Flow and Metabolism, 7, 729-738. 22. Giffard, R. G . , Monyer, H., Christine, C. W., Choi, D. W. (1990) 'Acidosis reduces NMDA receptor activation, glutamate neurotoxicity, and oxwen-ducose demivation neuronal injury in corfical cultures.' Brain Research, 506, 339-342. 23. Schallert. T . , Hernandez, T., Bath, T. M. (1986) 'Recovery of function after brain damage: severe and chronic disruption by
h
Mahagement of Epilepsy THEabolition of seizures without adverse
1018
effects is the most important goal in the treatment of epilepsy. Recognition of seizure types' and epileptic syndromes' is an essential component of both the choice of the appropriate anti-epileptic drug(s) (AED) and the calculation of the risk of recurrence should plans be made for the AED to be withdrawn after a period of freedom from seizure^^.^. After the initial seizure, the risk of recurrence of absence, atonic, atypical absence and myoclonic seizures, and of infantile spasms, is virtually 100 per cent, so it is simple to make a positive decision to introduce an AED at the time of diagnosis. For other seizure types, however, deciding when to start treatment may be more difficult. Persistent seizures are associated with loss of intellectual activity'. Delay in the institution of AEDs can be associated with greater difficulties in subsequent c ~ n t r o l ~ . ~ *but ' , introducing an AED after a first seizure does not necessarily prevent a recurrence'. The cumulative risks of recurrence have been variously computed to be 69 per cent if a non-febrile seizure occurs before the age of seven years'; 42 per cent over-all, but 60 per cent by three years if there is a 'remote symptomatic' aetiology''; and 52
diazepam.' Brain Research, 379, 104-1 I I . 24. Gorier, J . A., Veerman, M., Mirmiran, M., Bos, N. P., Corner, M. A. (1991) 'Spectral analysis of the electroencephalogram in neonatal rats chronically treated with the NMDA antagonist MK-801.' Developmental Brain Research, 64, 37-41. 25. Barth, T., Grant, M. L., Schallert, T. (1990) 'Effects of MK-801 on recovery from sensorimotor cortex lesions.' Stroke, 21 (Suppl. 3). 153-157.
26. Thiringer, K . , Hrbek, A . , Karlsson, K . , Rosen, K . , Kjellmer, I . (1987) 'Postasphyxial cerebral survival in newborn sheep after treatment with oxygen free radical scavengers and a calcium antagonist.' Pedialric Researcfi, 221, 62-66.
per cent if absence, akinetic and atonic seizures and infantile spasms are excluded'. 79 per cent of children having one recurrence will have further episodes'. There might be some justification for starting an AED after an initial seizure if there are abnormal neurological signs and/or epileptiform discharges on the EEG*>'O, but with few exceptions an AED is definitely indicated after the second unprovoked seizure. The exceptions are benign partial epijepsy with centrotemporal spikes, for which an AED is not essential"; and purely photosensitive seizures, where treatment by actual or functional occlusion of the vision to one eye during provocation can abolish the tendency to attacksI2. Drugs can be given continuously or intermittently during exacerbations of seizures. Intermittent diazepam (DZM) can be used as the sole drug for prophylaxis of febrile seizures, but only if there is apparent inefficacy of all drugs used for chronic therapy would intermittent DZM be considered as the sole AED for recurrent unprovoked seizures. Home-use of DZM has been established in the treatment of break-through serial and prolonged seizures in children on maintenance AEDS, resulting in very significant reductions in the use of emergency-room services and improvements in social a d j ~ s t m e n t ' ~Intermittent . DZM can also be very effective in the treatment of nonconvulsive status epilepticu~'~. Approximately 80 per cent of patients placed on chronic therapy will respond to a single AED, if used to maximum benefit',
therefore monotherapy is an important aim. Sodium valproate (VPA), carbamazepine (CBz) and phenytoin (PHT) are equally effective in the treatment of generalised tonic-clonic and partial seizuresI5-I7.Of these, VPA is the easiest to use, since once-daily dosing is possible; CBZ has a short half-life and needs to be given at least twice daily, even if a controlled-release formulation is prescribed; and PHT, with its saturation VPA kinetics, is the most pr~blematical'~. is thus the first choice; though caution should be exercised when treating children under two years who are developmentally delayed; if there is any possibility of a metabolic disorder involving liver enzyme activity, it would be wiser to use CBZ, PHT or even phenobarbitone (PB). VPA should be introduced gradually. An effect may not be obvious for two to three weeks after the maintenance dose is reached. If a more rapid response is desired, CBZ is likely to control seizures within 36 to 48 hours; alternatively, PHT or PB can be given as loading doses with subsequent maintenance treatment. Ethosuximide (ESM) is as effective as VPA in the treatment of typical absences. Juvenile myoclonic epilepsy is responsive only to VPA; which is also specifically indicated if photosensitivity is severe enough for AED treatment. I f the seizures of benign partiai epilepsy with centro-temporal spikes are very frequent or cause a lot of concern, CBZ is usually chosen. Infantile spasms, Lennox-Gastaut syndrome and other epilepsies resistant to first-line AEDS need a more considered approach. For idiopathic infantile spasms, ACTH or steroids should be given as soon as possible. When infantile spasms are symptomatic, the prescription of ACTH or steroids can rarely be justified; and, in addition to VPA (which may be effective in very high dosage18)and benzodiazepines (BD), vigabatrin (GVG)has recently been shown to be particularly helfpul". GVG can also be useful for Lennox-Gastaut syndrome, but has been found especially effective for cryptogenic partial epilepsy resistant to other AEDS, as well as for other refractory partial epilepsies, with or without secondary generalisation20.21. However, GVG may make non-progressive myoclonic epilepsies worse2'.
-
Atonic and atypical seizures are N 0 notoriously difficult to control. Lamo0 trigine (LTG) has reduced the frequencies 0 of such seizures in at least half the d m patients treated in open studies22. Myoclonic and generalised tonic-clonic seizures sometimes respond to LTG, and for adults, LTG has been found to be significantly effective for otherwise refractory partial seizures22. When introducing an AED, unless there is urgent need for loading, half the proposed maintenance dose should be h prescribed for a week or two before giving s the full amount. This is particularly important with CBZ, since toxic side-effects occur readily if too large a dose is used initially; and with LTG, since a sensitivity rash is more likely to occur if it is not introduced gradually2'. In the absence of overt multisystem disease, there is no indication for haematological or biochemical screening before commencement of an AED that has already received a product licence. Knowledge of the relevant pharmacokinetics is a prerequisite for the rational PHT monitoring of plasma AED has saturation kinetics, so plasma levels must be monitored after any change in d ~ s a g e ~ If~ -CBZ ~ ~ .is to be estimated, trough values-or those at a standard time of day-should be examined in relation to dosage24. Seizure control does not correlate meaningfully with plasma levels of BD, VPA and GVG, so it is not worth performing these estimations unless total non-compliance is suspected. A rapid assay service leads to more efficient m~nitoring~~. During treatment with AEDs, clinical observation is more important than routine haematological or biochemical assessment for the early detection of ~ i d e - e f f e c t s ~ ~ ~ ~ ~ ~ ~ . Transient adverse effects are very common during AED treatment28; approximately 20 per cent of regimes need to be discontinued. Unwanted effects are more common if multiple- rather than singledrug regimes are used. Reactions to VPA resulting in hyperammonaemia or hepatic failure are now believed to be secondary to inborn errors of m e t a b o l i ~ m ~The ~. most common side-effect of GVG is agitation, but drowsiness, insomnia and ataxia have also been reported2'. Psychosis 1019
--2
.-m
E
Q
may occur in adults given GVG. The only 8. Camfield, P. R., Camfield, C. S., Dooley, J . M., Tibbles, J. A. R., Fung, T., Garner, B. (1985) significant adverse effects of LTG is a ‘Epilepsy aftcr a first unprovoked seizure in rash, which is usually maculopapular, but childhood.’ Neurology, 35, 1657-1660. 9. Hirtz, D. G., Ellenberg, J. H., Nelson, K. B. may be erythema multiforme22. (1984) ‘The risk of recurrence of nonfebrile Approximately 70 per cent of children seizures in children.’ Neurology, 34, 637-641. will remain seizure-free if AEDS are 10. Shinnar, S., Berg, A. T., Moshe, S. L., Petix, M., Maytal, J., Kang, H., Goldensohn, E. S., withdrawn after at least two years without Hauser, W. A. (1990) ‘Risk of seizure recurattacks3’. Factors increasing the risk of ence followine. a first unorovoked seizure in recurrence are mental r e t a r d a t i ~ n ~ ~ , ~ ’ , childhood: a prospective siudy.’ Pedrairics, 85, IO7h-IORS .. - .- - - . seizure onset before two years3’, many 1 1 . Ambrosetto, G., Tassinari, C. (1990) ‘Antiseizures before c ~ n t r o l ~ *relatively ~~, pileptic drug treatment of benign childhood shorter periods without seizures before epilepsy with Rolandic spikes: is i t necessary?’ Epilepsia, 31, 802-805. remission4, abnormal EEG at time of 12. Wilkins, A,, Lindsay, J. (1985) ‘Common forms discontinuance of therapy30*3i, polyof reflex epilepsy: physiological mechanisms and techniques for treatment.’ In Pedley, therapy4 and previous infantile spasms3’, T. A., Meldrum, B. S. (Eds.) Recen! Advances or neonatal, myoclonic or ‘never generalin Epilepsy, No. 2. Edinburgh: Churchill ised’ partial seizures4. Juvenile myoclonic Livingstone. pp. 239-271. 13. Kriel, R. L., Cloyd, J . C., Hadsall, R. S., epilepsy always relapses if VPA is withCarlson, A. M., Floren, K. L., Jones-Saete, drawn. AEDS should always be reduced C. M. (1991) ‘Home use of rectal diazepam for gradually, one at a time for polytherapy, cluster and prolonged seizures: efficacy, adverse reactions, quality of life and cost with discontinuance after a few months. analysis.’ Pediatric Neurology, 7, 13-17. ’ A trial withdrawal is well worthwhile if 1. Lornbroso, C. T. (1989) ‘Intermittent home there are no significant risk factors, but treatment of status and clusters of seizures.’ Epilepsia, 30 (Suppl. 2), SI l-Sl4. unjudicious reduction of therapy can lead 5 . Brodie, M. J. (1990) ‘Established anticonto the recurrence of seizures and difficulty vulsants and treatment of refractory epilepsy.’ Lancet, 336, 350-354. in re-establishing control.
SHEILA J . WALLACE Consultant Paediatric Neurologist, University Hospital of Wales, Heath Park, Cardiff CF4 4X W .
1020
References I . Commission on Classification and Terminology of the International League Against Epilepsy (1981) ‘Proposal for revised clinical and electroencephalographic classification of epileptic seizures.’ Epilepsia, 22, 489-501. 2. Roger, J., Dravet, C., Bureau, M., Dreifuss, F. E., Wolf, P. (Eds.) (1985) Epilep!icSyndromes in Infancy, Childhood and Adolescence. London: John Libbey Eurotext. 3. Callaghan, N., Garrett, A., Goggin, T. (1988) ‘Withdrawal of anticonvulsant drugs in patients free of seizures for two years. A prospective study.’ New England Journal of Medicine, 318, 942-946. 4. Medical Research Council Antiepileptic Drug Withdrawal Study Group (1991) ‘Randomised study of antiepileptic drug withdrawal in patients in remission.’ Loncer, 337, 1175-1 180. 5. Holmes, G. L. (1991) ‘Do seizures cause brain damage?’ Epilepsia, 32 (Suppl. 9, S14-S28. 6. Camfield, P. R., Camfield, C. S., Smith, E. C., Tibbles, J . A. R. (1985) ‘Newly treated childhood epilepsy: a prospective study of recurrences and side-effects.’ Neurology, 35, 722-725. 7. Collaborative Group for the Study of Epilepsy (1992) ‘Prognosis of epilepsy in newly referred patients: a multicenter prospective study of the effects of monotherapy on the long-term course of epilepsy.’ Epilepsia, 33, 45-5 I.
6 . Rylance, G. W. (1990) ‘Treatment of epilepsy and febrile convulsions in children.’ Lance!, 336, 488-491. 17. de Silva, M., McArdle, B., McGowan, M., Reynolds, E. H., Neville, B., Johnson, A. L. (1989) ‘Monotherapy for newly diagnosed childhood epilepsy: a comparative trial and prognostic evaluation.’ Epilepsia, 30, 662. (A bsrracr.) 18. Prats, J. M., Garaizar, C., Rua, M. J., GarciaNieto, M: L., Madoz, P. (1991) ‘Infantile spasms treated with high doses of sodium valproate: initial response and follow-up.’ Developmen!al Medicine and Child Neurology, 33,61’7-625. 19. Chiron, C., Dulac, O . , Luna, D., Palacios, L., Mondragon, S., Beaumont, D., Mumford, J . P. (1990) ‘Vigabatrin in infantile spasms.’ Lance!, 335, 363-364. 20. Luna, D., Dulac, O., Pajot, N., Beaumont, D. (1989) ‘Vigabatrin in the treatment of childhood epilepsies: a single-blind placebocontrolled study.’ Epilepsia, 30, 430-437. 2t. Mumford, J . P., Lewis, P. J . (1991) ‘Vigabatrin.’ In Pisani, F., Perrucca, E., Avanzini, G., Richens, A. (Eds.) New A nriepileplic Drugs (Epilepsy Research, Suppl. 3. Amsterdam: Elsevier. pp. 161-168. 22. Yuen, A. W. C. (1991) ‘Lamotrigine.’ In Pisani, F., Perrucca, E., Avanzini, G., Richens, A. (Eds.) New Anriepileptic Drugs (Epilepsy Research, Suppl. 3). Amsterdam: Elsevier. pp. 115-123. 23. Wallace, S. J . (1990) ‘Anti-epileptic drug monitoring. An overview.’ Developmenral Medicine and Child Neurology, 32, 923-926. (Annotation.) 24. Brodie, M. J., Feely, J. (1988) ‘Practical clinical pharmacology. Therapeutic drug monitoring and clinical trials.’ Brirish Medical Journal, 296, 1 1 10-1 114.
25. Cosgrove, M., Pople, S., Wallace, S. J. (1990) ‘Rapid anti-epileptic drug assay.’ Developmental Medicine and Child Neurology, 32, 796-799. 26. Lancet, Ediroriul (1989) ‘Carbamazepine update.’ Lancer, 2, 595-597. 27. Dreifuss, F. E., Langer, D. H., Moline, K. A., Maxwell, J . E. (1989) ‘Valproic acid hepatic fatalities. II: US experience since 1984.’ Neurology, 39, 201-207. 28. Abu-Arafeh, I . A., Wallace, S. J. (1988! ‘Unwanted effects of anti-epileptic drugs. Developrnenral Medicine and Child Neurology, 30, 117-121. (Annofatton.)
29. Brown, J. K. (1988) ‘Valproate toxicity.’ Developmenral Medicine and Child Neurology, 30, 121-125. (Annotation.) 30. Emerson, R . , DSouza, B. J., Vining, E. P., Holden, K. R., Mellits, E. D., Freeman, J. M . (1981) ‘Stopping medication in children with eoileosv. Predictors of outcome.’ New Engianb Journal of Medicine, 304, 1125-1 129. 31. Matricardi, M., Brinciotti, M . , Benedetti, P. (1989) ‘Outcome after discontinuation of antiepileptic drug therapy in children with epilepsy.’ Epilepsia, 30, 582-589.
P
46th Annual Meeting of the American Epilepsy Society Seattle, 4th to loth December 1992 This meeting will be held at the Westin Hotel, Seattle. The scientific programme will commence on 7th December. Further information from the American Epilepsy Society, 638 Prospect Avenue, Hartford, Connecticut 06105-4298. Tel.: (203) 232 4835; Fax: (203) 232 0819.
Courses at Castle Priory College Wallingford, Autumn 1992 Atmospherics, 30th November to 1st December (28/235)*. Creating imaginative sensory environments with accessible ‘low-tech’ equipment, including an introduction to new concepts in group massage. Tutor: Sheena Laurent. f71.50. The Use of Multi-sensory Rooms, 19th October (28/186), 5th November (28/205), 2nd December (28/236)*. Concepts, enabling techniques and development of themes. For all interested persons concerned with the stimulation of multi-disabled and sensory-impaired children and adults. f39.60. ‘Courses 281235 and 28/236 may be taken as a package at the special price of f91.00 for nonresidential participants and f 114.50 for those wishing to stay overnight on 1st December. An Introduction to Conductive Education, 23rd to 25th October. For professionals and parents of cerebral-palsied children who have limited or no knowledge of this system and the principles which support it. Tutors: Olive Surtees and Maureen Lilley. Course 281190. €162.80. Behavioural Difficullies in Children with Special Needs, 30th October to 1st November. A workshop on behaviour modification, observation techniques and goal planning. Tutor: Malcolm Jones of Beech Tree School. Course 28/196; f162.80. Management of .Pupil Behaviour in Primary Classrooms, 10th to 12th November. A three-day course for teachers to prepare for the development
of a whole-school approach. Explores behavioural and psychodynamic approaches to behaviour, achieving objectivity through problem-solving and developing the skills of management and consultancy. Course 28/215; f203.50. Challenging Behaviour in the Classroom, 14th November. A one-day workshop on managing behaviours using structured programming. Led by Trevor Stevens, Oxford Training Consultants. Course 281219; f39.60. The Sherborne Movement Methodfor Children with Special Needs, 24th November. A workshop for staff working with children who have learning difficulties and/or physical disabilities. Course 281230; f 39.60. Perception-a Hidden Handicap? 27th to 29th November. For teachers, therapists and carers involved in helping children to cope with the effects of cerebral palsy, spina bifida, learning difficulties and non-specific handicaps. Tutor: Pat Kennedy. Course 281232; f162.80. The 24-hour Curriculum, 27th to 29th November. Support for and extension of classroom work is especially important for children and young people with severe learning problems. This programme is for teachers or care staff in residential schools, attached hostels, or leaders of parent organisations seeking to link daily living and curricular subjects. Tutor: Joyce Knowles. Course 281233; f 162.80. Challenging Behaviour: Programmes into, Action, 4th December. A level-2 course for those who wish to develop their work with challenging behaviours further. Participants should have attended a previous one-day workshop run by Oxford Training Consultants. Course 281241; f39.60. Supporting the Pupil with Dyslexia: Making the Curriculum Accessible, 7th December. Teachers, carers and parents welcomed. Course 281245; f39.60. Child Abuse and Special Needs, 1 Ith to 13th December. This course will be led by David Pithers, author of We Can Say No. Course 28/250; €162.80. For further details of courses and registration, contact: Castle Priory College, Wallingford, Oxfordshire OX10 OHE. Tel.: (0491) 37551/26350; Fax: (0491) 26359.
1021
h
Mahagement of Epilepsy THEabolition of seizures without adverse
1018
effects is the most important goal in the treatment of epilepsy. Recognition of seizure types' and epileptic syndromes' is an essential component of both the choice of the appropriate anti-epileptic drug(s) (AED) and the calculation of the risk of recurrence should plans be made for the AED to be withdrawn after a period of freedom from seizure^^.^. After the initial seizure, the risk of recurrence of absence, atonic, atypical absence and myoclonic seizures, and of infantile spasms, is virtually 100 per cent, so it is simple to make a positive decision to introduce an AED at the time of diagnosis. For other seizure types, however, deciding when to start treatment may be more difficult. Persistent seizures are associated with loss of intellectual activity'. Delay in the institution of AEDs can be associated with greater difficulties in subsequent c ~ n t r o l ~ . ~ *but ' , introducing an AED after a first seizure does not necessarily prevent a recurrence'. The cumulative risks of recurrence have been variously computed to be 69 per cent if a non-febrile seizure occurs before the age of seven years'; 42 per cent over-all, but 60 per cent by three years if there is a 'remote symptomatic' aetiology''; and 52
diazepam.' Brain Research, 379, 104-1 I I . 24. Gorier, J . A., Veerman, M., Mirmiran, M., Bos, N. P., Corner, M. A. (1991) 'Spectral analysis of the electroencephalogram in neonatal rats chronically treated with the NMDA antagonist MK-801.' Developmental Brain Research, 64, 37-41. 25. Barth, T., Grant, M. L., Schallert, T. (1990) 'Effects of MK-801 on recovery from sensorimotor cortex lesions.' Stroke, 21 (Suppl. 3). 153-157.
26. Thiringer, K . , Hrbek, A . , Karlsson, K . , Rosen, K . , Kjellmer, I . (1987) 'Postasphyxial cerebral survival in newborn sheep after treatment with oxygen free radical scavengers and a calcium antagonist.' Pedialric Researcfi, 221, 62-66.
per cent if absence, akinetic and atonic seizures and infantile spasms are excluded'. 79 per cent of children having one recurrence will have further episodes'. There might be some justification for starting an AED after an initial seizure if there are abnormal neurological signs and/or epileptiform discharges on the EEG*>'O, but with few exceptions an AED is definitely indicated after the second unprovoked seizure. The exceptions are benign partial epijepsy with centrotemporal spikes, for which an AED is not essential"; and purely photosensitive seizures, where treatment by actual or functional occlusion of the vision to one eye during provocation can abolish the tendency to attacksI2. Drugs can be given continuously or intermittently during exacerbations of seizures. Intermittent diazepam (DZM) can be used as the sole drug for prophylaxis of febrile seizures, but only if there is apparent inefficacy of all drugs used for chronic therapy would intermittent DZM be considered as the sole AED for recurrent unprovoked seizures. Home-use of DZM has been established in the treatment of break-through serial and prolonged seizures in children on maintenance AEDS, resulting in very significant reductions in the use of emergency-room services and improvements in social a d j ~ s t m e n t ' ~Intermittent . DZM can also be very effective in the treatment of nonconvulsive status epilepticu~'~. Approximately 80 per cent of patients placed on chronic therapy will respond to a single AED, if used to maximum benefit',
therefore monotherapy is an important aim. Sodium valproate (VPA), carbamazepine (CBz) and phenytoin (PHT) are equally effective in the treatment of generalised tonic-clonic and partial seizuresI5-I7.Of these, VPA is the easiest to use, since once-daily dosing is possible; CBZ has a short half-life and needs to be given at least twice daily, even if a controlled-release formulation is prescribed; and PHT, with its saturation VPA kinetics, is the most pr~blematical'~. is thus the first choice; though caution should be exercised when treating children under two years who are developmentally delayed; if there is any possibility of a metabolic disorder involving liver enzyme activity, it would be wiser to use CBZ, PHT or even phenobarbitone (PB). VPA should be introduced gradually. An effect may not be obvious for two to three weeks after the maintenance dose is reached. If a more rapid response is desired, CBZ is likely to control seizures within 36 to 48 hours; alternatively, PHT or PB can be given as loading doses with subsequent maintenance treatment. Ethosuximide (ESM) is as effective as VPA in the treatment of typical absences. Juvenile myoclonic epilepsy is responsive only to VPA; which is also specifically indicated if photosensitivity is severe enough for AED treatment. I f the seizures of benign partiai epilepsy with centro-temporal spikes are very frequent or cause a lot of concern, CBZ is usually chosen. Infantile spasms, Lennox-Gastaut syndrome and other epilepsies resistant to first-line AEDS need a more considered approach. For idiopathic infantile spasms, ACTH or steroids should be given as soon as possible. When infantile spasms are symptomatic, the prescription of ACTH or steroids can rarely be justified; and, in addition to VPA (which may be effective in very high dosage18)and benzodiazepines (BD), vigabatrin (GVG)has recently been shown to be particularly helfpul". GVG can also be useful for Lennox-Gastaut syndrome, but has been found especially effective for cryptogenic partial epilepsy resistant to other AEDS, as well as for other refractory partial epilepsies, with or without secondary generalisation20.21. However, GVG may make non-progressive myoclonic epilepsies worse2'.
-
Atonic and atypical seizures are N 0 notoriously difficult to control. Lamo0 trigine (LTG) has reduced the frequencies 0 of such seizures in at least half the d m patients treated in open studies22. Myoclonic and generalised tonic-clonic seizures sometimes respond to LTG, and for adults, LTG has been found to be significantly effective for otherwise refractory partial seizures22. When introducing an AED, unless there is urgent need for loading, half the proposed maintenance dose should be h prescribed for a week or two before giving s the full amount. This is particularly important with CBZ, since toxic side-effects occur readily if too large a dose is used initially; and with LTG, since a sensitivity rash is more likely to occur if it is not introduced gradually2'. In the absence of overt multisystem disease, there is no indication for haematological or biochemical screening before commencement of an AED that has already received a product licence. Knowledge of the relevant pharmacokinetics is a prerequisite for the rational PHT monitoring of plasma AED has saturation kinetics, so plasma levels must be monitored after any change in d ~ s a g e ~ If~ -CBZ ~ ~ .is to be estimated, trough values-or those at a standard time of day-should be examined in relation to dosage24. Seizure control does not correlate meaningfully with plasma levels of BD, VPA and GVG, so it is not worth performing these estimations unless total non-compliance is suspected. A rapid assay service leads to more efficient m~nitoring~~. During treatment with AEDs, clinical observation is more important than routine haematological or biochemical assessment for the early detection of ~ i d e - e f f e c t s ~ ~ ~ ~ ~ ~ ~ . Transient adverse effects are very common during AED treatment28; approximately 20 per cent of regimes need to be discontinued. Unwanted effects are more common if multiple- rather than singledrug regimes are used. Reactions to VPA resulting in hyperammonaemia or hepatic failure are now believed to be secondary to inborn errors of m e t a b o l i ~ m ~The ~. most common side-effect of GVG is agitation, but drowsiness, insomnia and ataxia have also been reported2'. Psychosis 1019
--2
.-m
E
Q
may occur in adults given GVG. The only 8. Camfield, P. R., Camfield, C. S., Dooley, J . M., Tibbles, J. A. R., Fung, T., Garner, B. (1985) significant adverse effects of LTG is a ‘Epilepsy aftcr a first unprovoked seizure in rash, which is usually maculopapular, but childhood.’ Neurology, 35, 1657-1660. 9. Hirtz, D. G., Ellenberg, J. H., Nelson, K. B. may be erythema multiforme22. (1984) ‘The risk of recurrence of nonfebrile Approximately 70 per cent of children seizures in children.’ Neurology, 34, 637-641. will remain seizure-free if AEDS are 10. Shinnar, S., Berg, A. T., Moshe, S. L., Petix, M., Maytal, J., Kang, H., Goldensohn, E. S., withdrawn after at least two years without Hauser, W. A. (1990) ‘Risk of seizure recurattacks3’. Factors increasing the risk of ence followine. a first unorovoked seizure in recurrence are mental r e t a r d a t i ~ n ~ ~ , ~ ’ , childhood: a prospective siudy.’ Pedrairics, 85, IO7h-IORS .. - .- - - . seizure onset before two years3’, many 1 1 . Ambrosetto, G., Tassinari, C. (1990) ‘Antiseizures before c ~ n t r o l ~ *relatively ~~, pileptic drug treatment of benign childhood shorter periods without seizures before epilepsy with Rolandic spikes: is i t necessary?’ Epilepsia, 31, 802-805. remission4, abnormal EEG at time of 12. Wilkins, A,, Lindsay, J. (1985) ‘Common forms discontinuance of therapy30*3i, polyof reflex epilepsy: physiological mechanisms and techniques for treatment.’ In Pedley, therapy4 and previous infantile spasms3’, T. A., Meldrum, B. S. (Eds.) Recen! Advances or neonatal, myoclonic or ‘never generalin Epilepsy, No. 2. Edinburgh: Churchill ised’ partial seizures4. Juvenile myoclonic Livingstone. pp. 239-271. 13. Kriel, R. L., Cloyd, J . C., Hadsall, R. S., epilepsy always relapses if VPA is withCarlson, A. M., Floren, K. L., Jones-Saete, drawn. AEDS should always be reduced C. M. (1991) ‘Home use of rectal diazepam for gradually, one at a time for polytherapy, cluster and prolonged seizures: efficacy, adverse reactions, quality of life and cost with discontinuance after a few months. analysis.’ Pediatric Neurology, 7, 13-17. ’ A trial withdrawal is well worthwhile if 1. Lornbroso, C. T. (1989) ‘Intermittent home there are no significant risk factors, but treatment of status and clusters of seizures.’ Epilepsia, 30 (Suppl. 2), SI l-Sl4. unjudicious reduction of therapy can lead 5 . Brodie, M. J. (1990) ‘Established anticonto the recurrence of seizures and difficulty vulsants and treatment of refractory epilepsy.’ Lancet, 336, 350-354. in re-establishing control.
SHEILA J . WALLACE Consultant Paediatric Neurologist, University Hospital of Wales, Heath Park, Cardiff CF4 4X W .
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References I . Commission on Classification and Terminology of the International League Against Epilepsy (1981) ‘Proposal for revised clinical and electroencephalographic classification of epileptic seizures.’ Epilepsia, 22, 489-501. 2. Roger, J., Dravet, C., Bureau, M., Dreifuss, F. E., Wolf, P. (Eds.) (1985) Epilep!icSyndromes in Infancy, Childhood and Adolescence. London: John Libbey Eurotext. 3. Callaghan, N., Garrett, A., Goggin, T. (1988) ‘Withdrawal of anticonvulsant drugs in patients free of seizures for two years. A prospective study.’ New England Journal of Medicine, 318, 942-946. 4. Medical Research Council Antiepileptic Drug Withdrawal Study Group (1991) ‘Randomised study of antiepileptic drug withdrawal in patients in remission.’ Loncer, 337, 1175-1 180. 5. Holmes, G. L. (1991) ‘Do seizures cause brain damage?’ Epilepsia, 32 (Suppl. 9, S14-S28. 6. Camfield, P. R., Camfield, C. S., Smith, E. C., Tibbles, J . A. R. (1985) ‘Newly treated childhood epilepsy: a prospective study of recurrences and side-effects.’ Neurology, 35, 722-725. 7. Collaborative Group for the Study of Epilepsy (1992) ‘Prognosis of epilepsy in newly referred patients: a multicenter prospective study of the effects of monotherapy on the long-term course of epilepsy.’ Epilepsia, 33, 45-5 I.
6 . Rylance, G. W. (1990) ‘Treatment of epilepsy and febrile convulsions in children.’ Lance!, 336, 488-491. 17. de Silva, M., McArdle, B., McGowan, M., Reynolds, E. H., Neville, B., Johnson, A. L. (1989) ‘Monotherapy for newly diagnosed childhood epilepsy: a comparative trial and prognostic evaluation.’ Epilepsia, 30, 662. (A bsrracr.) 18. Prats, J. M., Garaizar, C., Rua, M. J., GarciaNieto, M: L., Madoz, P. (1991) ‘Infantile spasms treated with high doses of sodium valproate: initial response and follow-up.’ Developmen!al Medicine and Child Neurology, 33,61’7-625. 19. Chiron, C., Dulac, O . , Luna, D., Palacios, L., Mondragon, S., Beaumont, D., Mumford, J . P. (1990) ‘Vigabatrin in infantile spasms.’ Lance!, 335, 363-364. 20. Luna, D., Dulac, O., Pajot, N., Beaumont, D. (1989) ‘Vigabatrin in the treatment of childhood epilepsies: a single-blind placebocontrolled study.’ Epilepsia, 30, 430-437. 2t. Mumford, J . P., Lewis, P. J . (1991) ‘Vigabatrin.’ In Pisani, F., Perrucca, E., Avanzini, G., Richens, A. (Eds.) New A nriepileplic Drugs (Epilepsy Research, Suppl. 3. Amsterdam: Elsevier. pp. 161-168. 22. Yuen, A. W. C. (1991) ‘Lamotrigine.’ In Pisani, F., Perrucca, E., Avanzini, G., Richens, A. (Eds.) New Anriepileptic Drugs (Epilepsy Research, Suppl. 3). Amsterdam: Elsevier. pp. 115-123. 23. Wallace, S. J . (1990) ‘Anti-epileptic drug monitoring. An overview.’ Developmenral Medicine and Child Neurology, 32, 923-926. (Annotation.) 24. Brodie, M. J., Feely, J. (1988) ‘Practical clinical pharmacology. Therapeutic drug monitoring and clinical trials.’ Brirish Medical Journal, 296, 1 1 10-1 114.
25. Cosgrove, M., Pople, S., Wallace, S. J. (1990) ‘Rapid anti-epileptic drug assay.’ Developmental Medicine and Child Neurology, 32, 796-799. 26. Lancet, Ediroriul (1989) ‘Carbamazepine update.’ Lancer, 2, 595-597. 27. Dreifuss, F. E., Langer, D. H., Moline, K. A., Maxwell, J . E. (1989) ‘Valproic acid hepatic fatalities. II: US experience since 1984.’ Neurology, 39, 201-207. 28. Abu-Arafeh, I . A., Wallace, S. J. (1988! ‘Unwanted effects of anti-epileptic drugs. Developrnenral Medicine and Child Neurology, 30, 117-121. (Annofatton.)
29. Brown, J. K. (1988) ‘Valproate toxicity.’ Developmenral Medicine and Child Neurology, 30, 121-125. (Annotation.) 30. Emerson, R . , DSouza, B. J., Vining, E. P., Holden, K. R., Mellits, E. D., Freeman, J. M . (1981) ‘Stopping medication in children with eoileosv. Predictors of outcome.’ New Engianb Journal of Medicine, 304, 1125-1 129. 31. Matricardi, M., Brinciotti, M . , Benedetti, P. (1989) ‘Outcome after discontinuation of antiepileptic drug therapy in children with epilepsy.’ Epilepsia, 30, 582-589.
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46th Annual Meeting of the American Epilepsy Society Seattle, 4th to loth December 1992 This meeting will be held at the Westin Hotel, Seattle. The scientific programme will commence on 7th December. Further information from the American Epilepsy Society, 638 Prospect Avenue, Hartford, Connecticut 06105-4298. Tel.: (203) 232 4835; Fax: (203) 232 0819.
Courses at Castle Priory College Wallingford, Autumn 1992 Atmospherics, 30th November to 1st December (28/235)*. Creating imaginative sensory environments with accessible ‘low-tech’ equipment, including an introduction to new concepts in group massage. Tutor: Sheena Laurent. f71.50. The Use of Multi-sensory Rooms, 19th October (28/186), 5th November (28/205), 2nd December (28/236)*. Concepts, enabling techniques and development of themes. For all interested persons concerned with the stimulation of multi-disabled and sensory-impaired children and adults. f39.60. ‘Courses 281235 and 28/236 may be taken as a package at the special price of f91.00 for nonresidential participants and f 114.50 for those wishing to stay overnight on 1st December. An Introduction to Conductive Education, 23rd to 25th October. For professionals and parents of cerebral-palsied children who have limited or no knowledge of this system and the principles which support it. Tutors: Olive Surtees and Maureen Lilley. Course 281190. €162.80. Behavioural Difficullies in Children with Special Needs, 30th October to 1st November. A workshop on behaviour modification, observation techniques and goal planning. Tutor: Malcolm Jones of Beech Tree School. Course 28/196; f162.80. Management of .Pupil Behaviour in Primary Classrooms, 10th to 12th November. A three-day course for teachers to prepare for the development
of a whole-school approach. Explores behavioural and psychodynamic approaches to behaviour, achieving objectivity through problem-solving and developing the skills of management and consultancy. Course 28/215; f203.50. Challenging Behaviour in the Classroom, 14th November. A one-day workshop on managing behaviours using structured programming. Led by Trevor Stevens, Oxford Training Consultants. Course 281219; f39.60. The Sherborne Movement Methodfor Children with Special Needs, 24th November. A workshop for staff working with children who have learning difficulties and/or physical disabilities. Course 281230; f 39.60. Perception-a Hidden Handicap? 27th to 29th November. For teachers, therapists and carers involved in helping children to cope with the effects of cerebral palsy, spina bifida, learning difficulties and non-specific handicaps. Tutor: Pat Kennedy. Course 281232; f162.80. The 24-hour Curriculum, 27th to 29th November. Support for and extension of classroom work is especially important for children and young people with severe learning problems. This programme is for teachers or care staff in residential schools, attached hostels, or leaders of parent organisations seeking to link daily living and curricular subjects. Tutor: Joyce Knowles. Course 281233; f 162.80. Challenging Behaviour: Programmes into, Action, 4th December. A level-2 course for those who wish to develop their work with challenging behaviours further. Participants should have attended a previous one-day workshop run by Oxford Training Consultants. Course 281241; f39.60. Supporting the Pupil with Dyslexia: Making the Curriculum Accessible, 7th December. Teachers, carers and parents welcomed. Course 281245; f39.60. Child Abuse and Special Needs, 1 Ith to 13th December. This course will be led by David Pithers, author of We Can Say No. Course 28/250; €162.80. For further details of courses and registration, contact: Castle Priory College, Wallingford, Oxfordshire OX10 OHE. Tel.: (0491) 37551/26350; Fax: (0491) 26359.
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