- Email: [email protected]
Abstracts from invited speakers
Abstracts from invited speakers 1 New developments in magnetic (MRI) of white matter disorders M 5 van der KNAAP Department of Child Neurology, Amsterdam, The Netherlands
resonance
Free University
imaging
Hospital,
During the last few years we have applied the MRI pattern recognition program to unclassified white matter disorders. This has led to the definition of two ‘new’ disease entities. Vacuolating leukoencephalopathy with subcortical cysts is an autosomal recessive disorder, characterized by early-infantile onset of macrocephaly and a delayed onset of neurological deterioration dominated by cerebellar ataxia. MRI shows a diffuse cerebral leukoencephalopathy with presence of subcortical cysts, always in the anterior temporal area, often also in the frontoparietal region. The abnormal white matter has a swollen aspect. The central white matter structures, including corpus callosum, internal capsule and brain stem are relatively preserved. Follow-up MRI shows a slowly progressive cerebral atrophy, superimposed on the swelling. The disease of vanishing white matter is also an autosomal recessive disorder, characterized by childhood onset neurological chronic deterioration, in most cases with additional periods of rapid deterioration following minor head traumas and infections accomparued by fever, sometimes even leading to unexplained coma. The neurological signs consist mainly of cerebellar ataxia and spasticity. MRI demonstrates a diffuse abnormality of the cerebral hemispheric white matter, in which over time increasing parts show signal characteristics of cerebrospinal fluid. Also MR spectroscopy shows signs of progressive rarefication and cystic degeneration of the white matter. In neither of these disorders, is the basic defect known. These studies show that MRI can have an important contribution in the detection and definition of new, so far unclassified, white matter disorders.
2 Magnetic response imaging (MRI) pattern recognition of white matter disorders M S van der KNAAP,’ J VALK’ ‘Department of Child Neurology; 2Department of Radiology, Free University Hospital, Amsterdam, The Netherlands
The sensitivity of MRI in detecting white matter abnormalities is well recognized. However, generally its specificity is underestimated. MRI pattern recognition is a way of evaluating images, based on the systemic assessment of a large number of items. The items include the normality or abnormality of many separate brain structures (white and grey matter), the signal behaviour of the abnormal areas on different pulse sequences, the homogeneity of the signal abnormalities, the demarcation, contrast enhancement, presence of atrophy and the change over time. Systematic application of this evaluation process to a large number of MRI investigations in white matter disorders with known basic defect has demonstrated that in many white matter disorders a more or less homogeneous pattern of abnormalities is observed. In our study, the first major distinguishing item appeared to involve the symmetry of the lesions. Inherited white matter disorders usually lead to symmetrical white matter abnormalities, whereas asymmetrical white matter abnormalities are usually found in acquired white matter disorders. Other major distinguishing items were the pattern of spread, the involvement of grey matter structures, and contrast enhancement. The observation that more or less constant patterns of MRI abnormalities, different from each other, are found in different white matter disorders implies that MRI contains diagnostic information and, if used as a diagnostic tool, can reduce the battery of necessary tests. The conclusion of our studies is that MRI pattern recognition can have a major contribution in the diagnostic work-up of white matter disorders.
3 A Swedish multicentre study of white matter diseasesin children P UVEBRANT, R KRlSTJANSDOl-HR Department of Paediatrics, Sahlgren East Gtiteborg, Sweden
University
Hospital,
The use of magnetic resonance imaging (MRI) has resulted in the detection of an increasing number of children with leukodystrophy-looking white matter. Laboratory tests and clinical presentation, however, do not always correspond to any known entity and the course is often not progressive. In a Swedish multicentre study MRI findings and clinical data from 155 children considered to have white matter abnormalities have been assessed by a group of child neurologists,
A22
Abstracts:
neuroradiologists and neurochemists during the period 1992-1997. Of the 155 children, 29 were found to have mainly grey matter affection and in 23 the group considered the MRI signal of the white matter normal at re-evaluation. A definitive or probable diagnosis was found in 44 children (mainly lysosomal and inflammatory), but in 59 children no diagnosis could be established. These 59 children with white matter abnormalities and no diagnosis are the focus of the study. A progressive course was found in 21 of them, probably representing hitherto unknown leukodystrophies. Two children had a relapsing-remitting course and in 16 it was difficult to establish if the course was progressive or stationary. The disease was definitely stationary in 18 children. Two macrocephalic children with white matter abnormalities had no neurological symptoms at the time of the study, both had been investigated because of large heads. This group of non-leukodystrophic white matter diseases probably have many different aetiologies, some of which may represent maldevelopment in the form of dys- or hypomyelination rather than demyelination. In order to delineate and characterize diseases and syndromes within this group, further investigations (clinical, radiological, electro-ophthalmological and neurochemical) have been performed, so far in 28 children with white matter diseases of unknown origin. Some preliminary results will be presented.
4 Magnetic resonance imaging (MRI) pattern of viral encephalitis in children J (ZISTERGAARD, T CHRISTENSEN Departments of Paediatrics and MR Research Centre, University Hospital of Aarhus, Denmark Due to differences in neural pathogenic mechanisms of certain viruses, the cerebral manifestations of viral infections in children are not uniform. Some viruses attack specific central nervous system cells, others tend to affect entire regions. From a pure clinical point of view it has not always been easy to differentiate between the various causative agents and the different pathogenic mechanisms, especially between the acute viral encephalitis and the acute disseminated encephalomyelitis (ADEM). In recent years in which MRI has been more accessible, identification and knowledge of specific MRI patterns have made it possible better to separate certain neuroviral diseases. In acute viral encephalitis the cerebral involvement is mostly within the cortical grey matter. ADEM has been regarded predominately as a disease of the white matter with perivenular inflammation and demyelination. Accordingly, serial MR recordings have shown that in ADEM T2 prolongation can be located within the subcortical white matter and periventricular areas as well as in the cerebellum and brain stem. However, high signal changes on T2weighted spin echo sequences are also found in the deep grey matter, especially in the globus pallidus, putamina and thalami and are then located nearly
26th
Meeting
Scandinavian
Neuropediatric
Society
symmetrically. The high-signal changes may resolve in some areas simultaneously with development of new changes in other areas. It is our impression from our series that in ADEM the T2 prolongation often starts within the deep grey matter and remains for a long time in the subcortical white matter areas.
5 Botulinum toxin in the treatment of cerebral palsy (CP) syndromes I AlJl-WRiiM~ Hospital for Children and Adolescents, University Helsinki, Finland
of
Botulinum toxin A (BTX-A) is a protein exotoxin derived from Clostridiuln botulinunz. When injected in purified form into muscle, BTX-A enters the cholinergic nerve endings and causes a dose-dependent chemical denervation. The resulting weakening of the injected muscle can be of therapeutic value if overactivity of the muscle was responsible for the functional impairment. Since the early 1990s BTX-A has been used in children with cerebral palsy. The doses used in children vary enormously. The optimal doses for individual muscles may have to be titrated. At the current level of knowledge the maximum safety limits per treatment session have been set only for Botox: 12 units/kg, total amount 300 units. For the other commercial product, Dysport, no such limits for children exist. The indications for the use of BTX-A in children have been preoperative evaluation, improvement of function and quality of movement, control of increasing spasticity or reduction of pain. The outcome is dependent on correct patient selection. Focal dynamic hyperactivity, young age, good body perception and motivation are favourable factors when the movement pattern is to be changed. Single treatment has limited long-term effect and in order to have a long-lasting or permanent change serial treatment may be needed. Assessing treatment effect requires objective measurements before and after BTX-A injection; the needed measurements depend on the functional level of the child and the indications and aims of the treatment. The minimum measurements in clinical use should include assessment of spasticity, passive and active range of movement, level and quality of the target function, evaluation of change by patient/parent/treating therapist and video recording. The reported side-effects of BTX-A treatment are either local (e.g. pain, too much muscular weakening) or systematic (e.g. allergic reactions, dysphagia, changes in bowel movements). No reports on the possible long-term side-effects of serial BTX-A treatment during childhood exist. The key to correct use of BTX-A is an experienced team with thorough knowledge of analysing and assessing function in children with cebreral palsy as well as on the phamakokinetics of BTX-A.
Abstracts
from
invited
A23
speakers
6 Cerebral palsy: Therapeutic electrical stimulation S A PEDERSEN Department of Paediatrics, Denmark
University
Hospital
Hvidovre,
Therapeutic electrical stimulation (TES) for the treatment of disuse muscle atrophy in children with cerebral palsy (Cl’) will be introduced. The symptoms are most often progressive over years with shortening and contractures of involved muscles and progressive distortion of joints. The imbalance of tone leaves the non-spastic antagonistic muscle overlengthened and weak. The concept of TES has been involved in adult sportsmedicine and space science. TES employs low level electrical stimulation applied at home during sleep. The physiological basis of TES has yet to be elucidated. Only a few controlled studies of long-term stimulation have been performed - some of these have shown beneficial effects. Different theories of action will be presented and the proposed stimulation patterns of different CP syndromes will be presented. It is very important to stress that the actual treatment is a supplement to the conventional treatment programme and will not replace or substitute other modalities. i Practical experience from the first treated patients in Denmark since January 1996 will be presented as will the design of a Danish placebo-controlled double-blind ongoing investigation in children with cerebral palsy. The early treatment concept of stimulation of weak muscles and the reduction of tone in spastic muscles will be discussed.
7 The place of new and old anti-epileptic drugs in the treatment of childhood epilepsy syndromes R E APPLETON The Roald Dahl EEG Unit, Alder Hey - Royal Liverpool Children’s (NHS) Trust, Liverpool, UK The primary and universally recognized aim of the treatment of epilepsy is to achieve complete seizure control with either no side-effects or side-effects which are acceptable to the patient and family using a single anti-epileptic drug (AED). This applies to all epilepsies irrespective of the epilepsy syndrome or underlying aetiology. The concept of the epilepsy syndrome in the classification of the paediatric epilepsies is largely accepted. One of the most useful practical implications of this syndromic classification is to identify the most appropriate AED for a specific syndrome. This is particularly useful for syndromes characterized by multiple seizure types matching or pairing the drug to the syndrome may preclude the use of multiple AEDs, thereby facilitating polytherapy. ‘monotherapy’ and minimizing
Currently, the clinician is in an increasing therapeutic dilemma - even confusion -being faced with a large number of epilepsy syndromes and an expanding range of new AEDs. Although the new AEDs appear to be effective with good tolerability, this is based on predominantly adult data, or at best, anecdotal paediatric data. The question faced by a clinician is no longer - ‘to prescribe or not prescribe’, but ‘what’ and ‘when’. How can and should clinicians reconcile their pride of wanting to use the newer drugs to maximize seizure control and minimize adverse effects in their patients, with their prejudice against prescribing these therapies because of limited information, licensing restrictions and financial implications.
8 Central nervous system-related adverse effects of anti-epileptic drugs P ULDALL Department of Neuropaediatrics, Copenhagen, Denmark
State University
Hospital,
Cognitive side-effects of chronic anti-epileptic drug treatment in children is a critical issue. Through better seizure control, improved development is often hoped for, but rarely documented. Animal studies have demonstrated that exposure to PB is harmful at an early age. Exposure of PB to children in &em and prophylactic for febrile convulsions seems to carry a high risk of persisting lower performance after discontinuation of PB. The very few existing well documented studies seem to indicate that the old anti-epileptic drugs (VPA, PB, CBZ, PI-IT) have rather little impact on the cognitive function of school children, and, if differences between these drugs exist, they are probably minor. The most convincing studies are, however, discontinued treatment studies and they cannot disclose slowly reversible or irreversible side-effects. The studies give the results of the group, not the single child with a possible metabolic defect. Small single case reports of serious dementia (among others VPA) highlights this problem. We have no studies of cognitive function in children on our new drugs (LTG, VGT, GET, TPM, OXC). In this situation it is recommended to be open to complaints of parents or teachers concerning suspicion of cognitive deterioration after starting anti-epileptic drug treatment. A trial to reduce or taper the drug, should be done even though other causes may be more obvious. Finally in a child with long-standing cognitive dysfunction the possibility should always be considered at some time of tapering the drug because of the possibilities of an insidious detrimental effect in a susceptible child. CBZ: Carbamazepine/clobamn; GPT: gabapentin; OXC: oxcarbazpin; PB: phenobarbitone; PHT: topiramate; VGT: vigabatrin; VPA: valproate.
LTG: lamotrigine; phenytoin; TPM:
A24
Abstracts:
9
Febrile seizures, to treat or not to treat: Results of 12 years’ follow-up F U KNUDSEN Department Denmark
of Paediatrics,
University
Hospital
Clostrup,
The long-term outcome of febrile seizures is generally benign. However, there are still some doubts as to whether febrile convulsions may be associated with a less benign outcome in more subtle aspects of intellectual and cognitive functions and there is an ongoing debate as to whether medical intervention can improve the longterm prognosis. The problem has been studied in a cohort of 289 children with febrile convulsions randomized in early childhood to either intermittent prophylaxis (diazepam at fever) or no prophylaxis (diazepam at seizures) and followed up 12 years later. Data include occurrence of epilepsy and neurological, motor, scholastic, intellectual and cognitive function in the cohort at the time of follow-up. By means of multivariate analysis a number of potential, prenatal and postnatal risk factors for adverse long-term outcome in febrile seizures is evaluated. At follow-up the two groups are of equal age (14 years). The cohort was studied with regard to occurrence of epilepsy, neurological function, fine and gross motor development (STOTT), intellectual performance on the Wechsler intelligence scale for children (verbal IQ, performance IQ and full scale IQ) as well as cognitive abilities on a neuropsychological test battery. The following risk factors were studied: Gender, birth
26th
Meeting
Scandinavian
Neuropediatric
Society
weight, afebrile and febrile seizures in the family, psychomotor retardation at the time of the first febrile seizure, febrile seizure type (simple and complex), the total number of febrile seizures, electroencephalogram findings at the time of first febrile seizure, social factors and type of treatment. The results are not yet available, but the long-term occurrence of epilepsy, motor, neurological, intellectual, cognitive and scholastic performance is not influenced by the type of treatment given in early childhood.
10
There is an intimate but complex relationship between epilepsy and autism L SAHLHOLDT Danish
Epilepsy
Hospital,
Dianalund,
Denmark
1. Autistic spectrum disorders are seen in approximately one-third of children with epilepsy and mental retardation. 2. Approximately one-third of autistic children have or have had epilepsy when they reach adulthood. 3. Autism is a well described sequela of infantile spasms and perhaps also of Lennox-Gastau syndrome. 4. Several case studies describe epilepsy presenting itself as autistic behaviour, e.g. long-lasting non-convulsive status epilepticus, Landau-Kleffner syndrome and CSWS (continuous spike-waves during slow-wave sleep). The autistic regression may in these cases be time-limited.
resonance
Free University
imaging
Hospital,
During the last few years we have applied the MRI pattern recognition program to unclassified white matter disorders. This has led to the definition of two ‘new’ disease entities. Vacuolating leukoencephalopathy with subcortical cysts is an autosomal recessive disorder, characterized by early-infantile onset of macrocephaly and a delayed onset of neurological deterioration dominated by cerebellar ataxia. MRI shows a diffuse cerebral leukoencephalopathy with presence of subcortical cysts, always in the anterior temporal area, often also in the frontoparietal region. The abnormal white matter has a swollen aspect. The central white matter structures, including corpus callosum, internal capsule and brain stem are relatively preserved. Follow-up MRI shows a slowly progressive cerebral atrophy, superimposed on the swelling. The disease of vanishing white matter is also an autosomal recessive disorder, characterized by childhood onset neurological chronic deterioration, in most cases with additional periods of rapid deterioration following minor head traumas and infections accomparued by fever, sometimes even leading to unexplained coma. The neurological signs consist mainly of cerebellar ataxia and spasticity. MRI demonstrates a diffuse abnormality of the cerebral hemispheric white matter, in which over time increasing parts show signal characteristics of cerebrospinal fluid. Also MR spectroscopy shows signs of progressive rarefication and cystic degeneration of the white matter. In neither of these disorders, is the basic defect known. These studies show that MRI can have an important contribution in the detection and definition of new, so far unclassified, white matter disorders.
2 Magnetic response imaging (MRI) pattern recognition of white matter disorders M S van der KNAAP,’ J VALK’ ‘Department of Child Neurology; 2Department of Radiology, Free University Hospital, Amsterdam, The Netherlands
The sensitivity of MRI in detecting white matter abnormalities is well recognized. However, generally its specificity is underestimated. MRI pattern recognition is a way of evaluating images, based on the systemic assessment of a large number of items. The items include the normality or abnormality of many separate brain structures (white and grey matter), the signal behaviour of the abnormal areas on different pulse sequences, the homogeneity of the signal abnormalities, the demarcation, contrast enhancement, presence of atrophy and the change over time. Systematic application of this evaluation process to a large number of MRI investigations in white matter disorders with known basic defect has demonstrated that in many white matter disorders a more or less homogeneous pattern of abnormalities is observed. In our study, the first major distinguishing item appeared to involve the symmetry of the lesions. Inherited white matter disorders usually lead to symmetrical white matter abnormalities, whereas asymmetrical white matter abnormalities are usually found in acquired white matter disorders. Other major distinguishing items were the pattern of spread, the involvement of grey matter structures, and contrast enhancement. The observation that more or less constant patterns of MRI abnormalities, different from each other, are found in different white matter disorders implies that MRI contains diagnostic information and, if used as a diagnostic tool, can reduce the battery of necessary tests. The conclusion of our studies is that MRI pattern recognition can have a major contribution in the diagnostic work-up of white matter disorders.
3 A Swedish multicentre study of white matter diseasesin children P UVEBRANT, R KRlSTJANSDOl-HR Department of Paediatrics, Sahlgren East Gtiteborg, Sweden
University
Hospital,
The use of magnetic resonance imaging (MRI) has resulted in the detection of an increasing number of children with leukodystrophy-looking white matter. Laboratory tests and clinical presentation, however, do not always correspond to any known entity and the course is often not progressive. In a Swedish multicentre study MRI findings and clinical data from 155 children considered to have white matter abnormalities have been assessed by a group of child neurologists,
A22
Abstracts:
neuroradiologists and neurochemists during the period 1992-1997. Of the 155 children, 29 were found to have mainly grey matter affection and in 23 the group considered the MRI signal of the white matter normal at re-evaluation. A definitive or probable diagnosis was found in 44 children (mainly lysosomal and inflammatory), but in 59 children no diagnosis could be established. These 59 children with white matter abnormalities and no diagnosis are the focus of the study. A progressive course was found in 21 of them, probably representing hitherto unknown leukodystrophies. Two children had a relapsing-remitting course and in 16 it was difficult to establish if the course was progressive or stationary. The disease was definitely stationary in 18 children. Two macrocephalic children with white matter abnormalities had no neurological symptoms at the time of the study, both had been investigated because of large heads. This group of non-leukodystrophic white matter diseases probably have many different aetiologies, some of which may represent maldevelopment in the form of dys- or hypomyelination rather than demyelination. In order to delineate and characterize diseases and syndromes within this group, further investigations (clinical, radiological, electro-ophthalmological and neurochemical) have been performed, so far in 28 children with white matter diseases of unknown origin. Some preliminary results will be presented.
4 Magnetic resonance imaging (MRI) pattern of viral encephalitis in children J (ZISTERGAARD, T CHRISTENSEN Departments of Paediatrics and MR Research Centre, University Hospital of Aarhus, Denmark Due to differences in neural pathogenic mechanisms of certain viruses, the cerebral manifestations of viral infections in children are not uniform. Some viruses attack specific central nervous system cells, others tend to affect entire regions. From a pure clinical point of view it has not always been easy to differentiate between the various causative agents and the different pathogenic mechanisms, especially between the acute viral encephalitis and the acute disseminated encephalomyelitis (ADEM). In recent years in which MRI has been more accessible, identification and knowledge of specific MRI patterns have made it possible better to separate certain neuroviral diseases. In acute viral encephalitis the cerebral involvement is mostly within the cortical grey matter. ADEM has been regarded predominately as a disease of the white matter with perivenular inflammation and demyelination. Accordingly, serial MR recordings have shown that in ADEM T2 prolongation can be located within the subcortical white matter and periventricular areas as well as in the cerebellum and brain stem. However, high signal changes on T2weighted spin echo sequences are also found in the deep grey matter, especially in the globus pallidus, putamina and thalami and are then located nearly
26th
Meeting
Scandinavian
Neuropediatric
Society
symmetrically. The high-signal changes may resolve in some areas simultaneously with development of new changes in other areas. It is our impression from our series that in ADEM the T2 prolongation often starts within the deep grey matter and remains for a long time in the subcortical white matter areas.
5 Botulinum toxin in the treatment of cerebral palsy (CP) syndromes I AlJl-WRiiM~ Hospital for Children and Adolescents, University Helsinki, Finland
of
Botulinum toxin A (BTX-A) is a protein exotoxin derived from Clostridiuln botulinunz. When injected in purified form into muscle, BTX-A enters the cholinergic nerve endings and causes a dose-dependent chemical denervation. The resulting weakening of the injected muscle can be of therapeutic value if overactivity of the muscle was responsible for the functional impairment. Since the early 1990s BTX-A has been used in children with cerebral palsy. The doses used in children vary enormously. The optimal doses for individual muscles may have to be titrated. At the current level of knowledge the maximum safety limits per treatment session have been set only for Botox: 12 units/kg, total amount 300 units. For the other commercial product, Dysport, no such limits for children exist. The indications for the use of BTX-A in children have been preoperative evaluation, improvement of function and quality of movement, control of increasing spasticity or reduction of pain. The outcome is dependent on correct patient selection. Focal dynamic hyperactivity, young age, good body perception and motivation are favourable factors when the movement pattern is to be changed. Single treatment has limited long-term effect and in order to have a long-lasting or permanent change serial treatment may be needed. Assessing treatment effect requires objective measurements before and after BTX-A injection; the needed measurements depend on the functional level of the child and the indications and aims of the treatment. The minimum measurements in clinical use should include assessment of spasticity, passive and active range of movement, level and quality of the target function, evaluation of change by patient/parent/treating therapist and video recording. The reported side-effects of BTX-A treatment are either local (e.g. pain, too much muscular weakening) or systematic (e.g. allergic reactions, dysphagia, changes in bowel movements). No reports on the possible long-term side-effects of serial BTX-A treatment during childhood exist. The key to correct use of BTX-A is an experienced team with thorough knowledge of analysing and assessing function in children with cebreral palsy as well as on the phamakokinetics of BTX-A.
Abstracts
from
invited
A23
speakers
6 Cerebral palsy: Therapeutic electrical stimulation S A PEDERSEN Department of Paediatrics, Denmark
University
Hospital
Hvidovre,
Therapeutic electrical stimulation (TES) for the treatment of disuse muscle atrophy in children with cerebral palsy (Cl’) will be introduced. The symptoms are most often progressive over years with shortening and contractures of involved muscles and progressive distortion of joints. The imbalance of tone leaves the non-spastic antagonistic muscle overlengthened and weak. The concept of TES has been involved in adult sportsmedicine and space science. TES employs low level electrical stimulation applied at home during sleep. The physiological basis of TES has yet to be elucidated. Only a few controlled studies of long-term stimulation have been performed - some of these have shown beneficial effects. Different theories of action will be presented and the proposed stimulation patterns of different CP syndromes will be presented. It is very important to stress that the actual treatment is a supplement to the conventional treatment programme and will not replace or substitute other modalities. i Practical experience from the first treated patients in Denmark since January 1996 will be presented as will the design of a Danish placebo-controlled double-blind ongoing investigation in children with cerebral palsy. The early treatment concept of stimulation of weak muscles and the reduction of tone in spastic muscles will be discussed.
7 The place of new and old anti-epileptic drugs in the treatment of childhood epilepsy syndromes R E APPLETON The Roald Dahl EEG Unit, Alder Hey - Royal Liverpool Children’s (NHS) Trust, Liverpool, UK The primary and universally recognized aim of the treatment of epilepsy is to achieve complete seizure control with either no side-effects or side-effects which are acceptable to the patient and family using a single anti-epileptic drug (AED). This applies to all epilepsies irrespective of the epilepsy syndrome or underlying aetiology. The concept of the epilepsy syndrome in the classification of the paediatric epilepsies is largely accepted. One of the most useful practical implications of this syndromic classification is to identify the most appropriate AED for a specific syndrome. This is particularly useful for syndromes characterized by multiple seizure types matching or pairing the drug to the syndrome may preclude the use of multiple AEDs, thereby facilitating polytherapy. ‘monotherapy’ and minimizing
Currently, the clinician is in an increasing therapeutic dilemma - even confusion -being faced with a large number of epilepsy syndromes and an expanding range of new AEDs. Although the new AEDs appear to be effective with good tolerability, this is based on predominantly adult data, or at best, anecdotal paediatric data. The question faced by a clinician is no longer - ‘to prescribe or not prescribe’, but ‘what’ and ‘when’. How can and should clinicians reconcile their pride of wanting to use the newer drugs to maximize seizure control and minimize adverse effects in their patients, with their prejudice against prescribing these therapies because of limited information, licensing restrictions and financial implications.
8 Central nervous system-related adverse effects of anti-epileptic drugs P ULDALL Department of Neuropaediatrics, Copenhagen, Denmark
State University
Hospital,
Cognitive side-effects of chronic anti-epileptic drug treatment in children is a critical issue. Through better seizure control, improved development is often hoped for, but rarely documented. Animal studies have demonstrated that exposure to PB is harmful at an early age. Exposure of PB to children in &em and prophylactic for febrile convulsions seems to carry a high risk of persisting lower performance after discontinuation of PB. The very few existing well documented studies seem to indicate that the old anti-epileptic drugs (VPA, PB, CBZ, PI-IT) have rather little impact on the cognitive function of school children, and, if differences between these drugs exist, they are probably minor. The most convincing studies are, however, discontinued treatment studies and they cannot disclose slowly reversible or irreversible side-effects. The studies give the results of the group, not the single child with a possible metabolic defect. Small single case reports of serious dementia (among others VPA) highlights this problem. We have no studies of cognitive function in children on our new drugs (LTG, VGT, GET, TPM, OXC). In this situation it is recommended to be open to complaints of parents or teachers concerning suspicion of cognitive deterioration after starting anti-epileptic drug treatment. A trial to reduce or taper the drug, should be done even though other causes may be more obvious. Finally in a child with long-standing cognitive dysfunction the possibility should always be considered at some time of tapering the drug because of the possibilities of an insidious detrimental effect in a susceptible child. CBZ: Carbamazepine/clobamn; GPT: gabapentin; OXC: oxcarbazpin; PB: phenobarbitone; PHT: topiramate; VGT: vigabatrin; VPA: valproate.
LTG: lamotrigine; phenytoin; TPM:
A24
Abstracts:
9
Febrile seizures, to treat or not to treat: Results of 12 years’ follow-up F U KNUDSEN Department Denmark
of Paediatrics,
University
Hospital
Clostrup,
The long-term outcome of febrile seizures is generally benign. However, there are still some doubts as to whether febrile convulsions may be associated with a less benign outcome in more subtle aspects of intellectual and cognitive functions and there is an ongoing debate as to whether medical intervention can improve the longterm prognosis. The problem has been studied in a cohort of 289 children with febrile convulsions randomized in early childhood to either intermittent prophylaxis (diazepam at fever) or no prophylaxis (diazepam at seizures) and followed up 12 years later. Data include occurrence of epilepsy and neurological, motor, scholastic, intellectual and cognitive function in the cohort at the time of follow-up. By means of multivariate analysis a number of potential, prenatal and postnatal risk factors for adverse long-term outcome in febrile seizures is evaluated. At follow-up the two groups are of equal age (14 years). The cohort was studied with regard to occurrence of epilepsy, neurological function, fine and gross motor development (STOTT), intellectual performance on the Wechsler intelligence scale for children (verbal IQ, performance IQ and full scale IQ) as well as cognitive abilities on a neuropsychological test battery. The following risk factors were studied: Gender, birth
26th
Meeting
Scandinavian
Neuropediatric
Society
weight, afebrile and febrile seizures in the family, psychomotor retardation at the time of the first febrile seizure, febrile seizure type (simple and complex), the total number of febrile seizures, electroencephalogram findings at the time of first febrile seizure, social factors and type of treatment. The results are not yet available, but the long-term occurrence of epilepsy, motor, neurological, intellectual, cognitive and scholastic performance is not influenced by the type of treatment given in early childhood.
10
There is an intimate but complex relationship between epilepsy and autism L SAHLHOLDT Danish
Epilepsy
Hospital,
Dianalund,
Denmark
1. Autistic spectrum disorders are seen in approximately one-third of children with epilepsy and mental retardation. 2. Approximately one-third of autistic children have or have had epilepsy when they reach adulthood. 3. Autism is a well described sequela of infantile spasms and perhaps also of Lennox-Gastau syndrome. 4. Several case studies describe epilepsy presenting itself as autistic behaviour, e.g. long-lasting non-convulsive status epilepticus, Landau-Kleffner syndrome and CSWS (continuous spike-waves during slow-wave sleep). The autistic regression may in these cases be time-limited.