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Combined EEG and MEG analysis in epilepsy and cortical malformations
european journal of paediatric neurology 12, suppl. 1 (2008) S11–S19
Official Journal of the European Paediatric Neurology Society
16th May 2008 (Friday) 08.15 10.00 Plenary session: Progress in diagnosis of neurological disorders in childhood INV24 Advanced neuroimaging in pediatric neurological disorders H.T. Chugani. Division of Pediatric Neurology, PET Center, Children’s Hospital of Michigan, Detroit, Michigan, USA Although PET scanning with FDG is performed in older children, studies in sick newborns are less practical. Therefore, we installed the Focus 220 animal microPET scanner in our NICU. Preliminary studies documented the high spatial resolution (<2 mm full-width-at-half-maximum). Patterns of abnormal glucose metabolism in thalamus and basal ganglia predicted later types of cerebral palsy. PET scanning using alpha-methyl-L-tryptophan (AMT) in autistic children reveal a typical pattern of decreased AMT accumulation in left frontal cortex and thalamus, but elevated AMT accumulation in right cerebellum. For nonautistic children, serotonin synthesis capacity was >200% of adult values until about 5 years and then declined. In autistic children, serotonin synthesis capacity increased between 2−15 years to values 1.5 times of adult values. These data indicate a period of high brain serotonin synthesis capacity during childhood, which is disrupted in autistic children. These findings may be useful in monitoring interventions. We have recently applied AMT PET in patients with Tourette syndrome (TS), to study abnormal neurotransmission in the striatal-thalamo-cortical circuitry. Both cortical and subcortical abnormalities of tryptophan metabolism were found. Increased right caudate tryptophan uptake was associated with severe motor tics while abnormal AMT uptake in caudate/putamen were related to ADD. The findings support the role of serotonergic mechanisms in the pathophysiology of TS and co-morbid conditions. The combination of PET and MRI can prove to be powerful. For example, MR-DTI has been used to study plasticity of the contralateral optic radiation following unilateral occipital resection. Fractional anisotropy, apparent diffusion coefficient and number of fibers in the contralateral optic radiation all underwent significant plasticity changes following unilateral occipital resection. Examples will be provided as to how multimodality neuroimaging can be beneficial in children with neurological disorders.
INV25 Challenges of neonatal EEG K. Edebol Eeg-Olofsson. Section of Clinical Neurophysiology, Department of Neuroscience, University Hospital, Uppsala, Sweden The indications for performing neonatal EEG in newborn babies are mainly seizures or seizure-suspect events. Neonatal seizures are serious, mortality is 15−40%, and there is a high risk for neurological sequelae as well as of developing epilepsy. Electrical seizure activity is rare before gestational age 34−35 weeks. Some seizures do not have corresponding ictal seizure activity in the EEG. However, some seizure types are more often correlated to ictal seizure activity in the EEG, for example multifocal and focal seizures and focal tonic seizures. All electrical seizure activity has a focal start except for some generalised activity associated with myoclonic seizures or epileptic spasms. EEG abnormalities and ictal seizure activity in the EEG are associated with a worse prognosis compared to normal EEG findings, especially in premature neonates. The background activity in the EEG can serve as a prognostic marker; a normal background activity favours a better prognosis. Neonatal EEG also gives information about degree of maturity for gestational age, for example by showing absent or delayed normal features for age in delayed maturation, or disturbance of background activity. In order to interpret a neonatal EEG recording in an optimal way, it is crucial that the recording has a technical good quality and preferably is a polygraphic recording which enables the interpreter to consider the different sleep stages, which differ as to EEG patterns. Cerebral function monitoring (CFM), in newborns with seizures, has over the last few years become a practical tool in neonatal intensive care units, and amplitude-integrated EEG (A-EEG) is much used. Both standard digital EEG (9 or 12 electrodes, polygraphic recording, and video) and CFM (2 electrodes against a reference) are together the methods of choice in neonatal EEG. INV26 Combined EEG and MEG analysis in epilepsy and cortical malformations T. Bast. University Children’s Hospital, Heidelberg, Germany Malformations of cortical development (MCD) are a frequent cause of pharmacoresistent epilepsy. An increasing number of patients with MCD is identified by improved structural imaging and referred to presurgical evaluation. Inverse source analysis of MEG and EEG signals is a non-invasive diagnostic tool with a high temporal resolution and satisfying localization accuracy. It is applied to analyses of interictal and ictal epileptiform and physiologic, event related activities. MEG and EEG sources of interictal spikes localize within or nearby cortical malformations identified by MRI in most
1090-3798/ $ – see front matter © 2008 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
S12
16th May 2008 (Friday), Oral presentations 10.30−12.00
cases, reflecting intrinsic epileptogenicity. This non-invasive analysis may provide important information in the diagnostic work-up of patients with cryptogenic focal epilepsies, in which a high proportion suffers from discrete focal cortical dysplasia. Various studies have demonstrated the usefulness of a combination of EEG with MEG. MEG has some advantages over EEG. A lower influence of volume conduction results in a higher localization accuracy. Differences in signal-to-noise ratio lead to higher spike detection rates in MEG compared to EEG. However, MEG is almost exclusively sensitive to signals from tangential and oblique sources and mainly reflects activities from fissural or basal pyramidal cells. In contrast, EEG depicts activities from sources with variable orientations. EEG signals are dominated by activities of neurons with radial orientation located in the gyral crowns. Cortical malformations may lead to anatomical changes with abnormal gyration, thus resulting in marked differences between EEG and MEG analysis. The general recommendation of simultaneous recordings especially applies for patients with MCD.
10.30−12.00 Childhood multiple sclerosis INV27 Pediatric multiple sclerosis long story
a short history of a
F. Hanefeld. Department of Pediatrics and Pediatric Neurology, Georg-August-University Goettingen, Germany Shortly after multiple sclerosis (MS) was described by Charcot in 1872 1873, symptoms of MS were noted in children. At the time of these observations (late 19th century) the many inherited demyelinating diseases that manifest during childhood had not yet been recognized. Once the inherited demyelinating disorders became known, MS as a childhood disease was dismissed as a possible diagnosis. Only a half century later, with increased understanding of both inherited leukodystrophies as well as MS, was it acknowledged that children can develop MS. Our present challenges in the differential diagnoses of demyelinating disorders presenting in childhood, are reflected in the history of pediatric MS. INV28 How good are the McDonald criteria for childhood MS? D. Pohl. Department of Paediatrics and Paediatric Neurology, Georg-August-University, Robert-Koch-Strasse 40, 37075, Gottingen, Germany ¨ Since there is no simple test to secure the diagnosis of multiple sclerosis (MS), diagnostic criteria have been created including a combination of clinical and paraclinical studies. Whereas the old Poser-criteria required evidence of two clinical disease attacks for the diagnosis of definite MS, the McDonald criteria of 2001 included paraclinical evidence of dissemination in time via MRI and principally enabled a diagnosis of MS as early as 3 months after a single attack. In 2005, a revision of the McDonald Criteria was created with the aim of speeding diagnosis. The minimum interval for paraclinical dissemination in time was defined even shorter, enabling a diagnosis of MS if new T2 lesions develop later than one month after the beginning of a first attack. No definition of acute disseminated encephalomyelitis (ADEM) was included in the original McDonald criteria, and the revised McDonald criteria question the existence of ADEM as a separate entity from MS, thereby circumventing the diagnostic dilemma MS versus ADEM. The McDonald criteria state that they would best apply to individuals between 10 and 59 years of age, thus including juvenile MS and
excluding true childhood MS. ADEM is considered to be more prevalent in children than in adults, and is a major differential diagnosis of pediatric MS. The crucial question with regard to the applicability of the (revised) McDonald criteria is thus whether they allow a reliable diagnosis of pediatric MS, or if the rather liberal definition of dissemination in time might lead to the false diagnosis of MS in children with ADEM. This issue has to be urgently addressed, but until definite disease markers will be identified, only prospective longitudinal studies over periods as long as possible, ideally at least a decade, will be able to conclusively determine the validity of the McDonald criteria for pediatric MS. INV29 Treatment of childhood multiple sclerosis B. Anlar. Hacettepe University, Ankara, Turkey Treatment decisions in childhood MS are usually extrapolated from adult data. However several aspects of childhood MS differ considerably from adults, casting doubt on the validity of medical decisions. Diagnostic criteria and natural course of the disorder have not been validated in children. Therefore, disease-modifying therapies aiming at ameliorating the course of MS in childhood need to be justified. Acute demyelinating attacks are treated with glucocorticoids which hasten clinical recovery and resolution of gadoliniumpositive MRI lesions. Because abrupt discontinuation can result in relapses, oral taper over weeks is recommended as in acute disseminated encephalomyelitis. Attacks with sensory symptoms only, or those recovering already need no specific treatment. Disease-modifying therapies: Beta Interferons and Glatiramer acetate have been used in children. However they are not marketed and their doses are not defined for children. A reduced rate of relapses during follow-up of 2−3 years have been reported to date. Currently the limited nature of the data vs. the possibly higher efficacy of these drugs when used early appear to distance the clinician from evidence-based medicine.
10.30−12.00 Epilepsy preventive measures INV30 First epileptic seizure: to treat or not to treat? A. Covanis. Neurology Department, Agia Sophia Children’s Hospital, Athens, Greece Epileptic seizures are symptoms that occur in acute illness (provoked seizures linked to a specific trigger) or in epilepsy (unprovoked seizures with no obvious precipitating factor) and result from hyperexcitability, that is an imbalance between excitatory and inhibitory activity, of the cerebral neurons. Provoked seizures may be caused by, for example, metabolic disorders, febrile state, head trauma, stroke, drugs and alcohol withdrawal, which if present, preclude the diagnosis of an unprovoked episode. Furthermore, a variety of different paroxysmal events can in childhood be provoked by anger, frustration, stress, sleep deprivation or sleep, arousal, standing, bathing, menstruation, hyperventilation, chronic fatigue, alcohol, the use of illicit drugs in adolescence and are easily confused with seizures. In childhood all type of epileptic seizures are seen: epileptic spasms, typical and atypical absences, tonic, atonic, myoclonic and tonic clonic seizures and focal seizures. Some seizures are specific in childhood such as rolandic, autonomic, childhood absence seizures, tonic, atonic, astatic. The epileptic seizures, convulsive and non-convulsive, are generalised where the whole cerebral cortex or brain is involved and focal where
Official Journal of the European Paediatric Neurology Society
16th May 2008 (Friday) 08.15 10.00 Plenary session: Progress in diagnosis of neurological disorders in childhood INV24 Advanced neuroimaging in pediatric neurological disorders H.T. Chugani. Division of Pediatric Neurology, PET Center, Children’s Hospital of Michigan, Detroit, Michigan, USA Although PET scanning with FDG is performed in older children, studies in sick newborns are less practical. Therefore, we installed the Focus 220 animal microPET scanner in our NICU. Preliminary studies documented the high spatial resolution (<2 mm full-width-at-half-maximum). Patterns of abnormal glucose metabolism in thalamus and basal ganglia predicted later types of cerebral palsy. PET scanning using alpha-methyl-L-tryptophan (AMT) in autistic children reveal a typical pattern of decreased AMT accumulation in left frontal cortex and thalamus, but elevated AMT accumulation in right cerebellum. For nonautistic children, serotonin synthesis capacity was >200% of adult values until about 5 years and then declined. In autistic children, serotonin synthesis capacity increased between 2−15 years to values 1.5 times of adult values. These data indicate a period of high brain serotonin synthesis capacity during childhood, which is disrupted in autistic children. These findings may be useful in monitoring interventions. We have recently applied AMT PET in patients with Tourette syndrome (TS), to study abnormal neurotransmission in the striatal-thalamo-cortical circuitry. Both cortical and subcortical abnormalities of tryptophan metabolism were found. Increased right caudate tryptophan uptake was associated with severe motor tics while abnormal AMT uptake in caudate/putamen were related to ADD. The findings support the role of serotonergic mechanisms in the pathophysiology of TS and co-morbid conditions. The combination of PET and MRI can prove to be powerful. For example, MR-DTI has been used to study plasticity of the contralateral optic radiation following unilateral occipital resection. Fractional anisotropy, apparent diffusion coefficient and number of fibers in the contralateral optic radiation all underwent significant plasticity changes following unilateral occipital resection. Examples will be provided as to how multimodality neuroimaging can be beneficial in children with neurological disorders.
INV25 Challenges of neonatal EEG K. Edebol Eeg-Olofsson. Section of Clinical Neurophysiology, Department of Neuroscience, University Hospital, Uppsala, Sweden The indications for performing neonatal EEG in newborn babies are mainly seizures or seizure-suspect events. Neonatal seizures are serious, mortality is 15−40%, and there is a high risk for neurological sequelae as well as of developing epilepsy. Electrical seizure activity is rare before gestational age 34−35 weeks. Some seizures do not have corresponding ictal seizure activity in the EEG. However, some seizure types are more often correlated to ictal seizure activity in the EEG, for example multifocal and focal seizures and focal tonic seizures. All electrical seizure activity has a focal start except for some generalised activity associated with myoclonic seizures or epileptic spasms. EEG abnormalities and ictal seizure activity in the EEG are associated with a worse prognosis compared to normal EEG findings, especially in premature neonates. The background activity in the EEG can serve as a prognostic marker; a normal background activity favours a better prognosis. Neonatal EEG also gives information about degree of maturity for gestational age, for example by showing absent or delayed normal features for age in delayed maturation, or disturbance of background activity. In order to interpret a neonatal EEG recording in an optimal way, it is crucial that the recording has a technical good quality and preferably is a polygraphic recording which enables the interpreter to consider the different sleep stages, which differ as to EEG patterns. Cerebral function monitoring (CFM), in newborns with seizures, has over the last few years become a practical tool in neonatal intensive care units, and amplitude-integrated EEG (A-EEG) is much used. Both standard digital EEG (9 or 12 electrodes, polygraphic recording, and video) and CFM (2 electrodes against a reference) are together the methods of choice in neonatal EEG. INV26 Combined EEG and MEG analysis in epilepsy and cortical malformations T. Bast. University Children’s Hospital, Heidelberg, Germany Malformations of cortical development (MCD) are a frequent cause of pharmacoresistent epilepsy. An increasing number of patients with MCD is identified by improved structural imaging and referred to presurgical evaluation. Inverse source analysis of MEG and EEG signals is a non-invasive diagnostic tool with a high temporal resolution and satisfying localization accuracy. It is applied to analyses of interictal and ictal epileptiform and physiologic, event related activities. MEG and EEG sources of interictal spikes localize within or nearby cortical malformations identified by MRI in most
1090-3798/ $ – see front matter © 2008 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
S12
16th May 2008 (Friday), Oral presentations 10.30−12.00
cases, reflecting intrinsic epileptogenicity. This non-invasive analysis may provide important information in the diagnostic work-up of patients with cryptogenic focal epilepsies, in which a high proportion suffers from discrete focal cortical dysplasia. Various studies have demonstrated the usefulness of a combination of EEG with MEG. MEG has some advantages over EEG. A lower influence of volume conduction results in a higher localization accuracy. Differences in signal-to-noise ratio lead to higher spike detection rates in MEG compared to EEG. However, MEG is almost exclusively sensitive to signals from tangential and oblique sources and mainly reflects activities from fissural or basal pyramidal cells. In contrast, EEG depicts activities from sources with variable orientations. EEG signals are dominated by activities of neurons with radial orientation located in the gyral crowns. Cortical malformations may lead to anatomical changes with abnormal gyration, thus resulting in marked differences between EEG and MEG analysis. The general recommendation of simultaneous recordings especially applies for patients with MCD.
10.30−12.00 Childhood multiple sclerosis INV27 Pediatric multiple sclerosis long story
a short history of a
F. Hanefeld. Department of Pediatrics and Pediatric Neurology, Georg-August-University Goettingen, Germany Shortly after multiple sclerosis (MS) was described by Charcot in 1872 1873, symptoms of MS were noted in children. At the time of these observations (late 19th century) the many inherited demyelinating diseases that manifest during childhood had not yet been recognized. Once the inherited demyelinating disorders became known, MS as a childhood disease was dismissed as a possible diagnosis. Only a half century later, with increased understanding of both inherited leukodystrophies as well as MS, was it acknowledged that children can develop MS. Our present challenges in the differential diagnoses of demyelinating disorders presenting in childhood, are reflected in the history of pediatric MS. INV28 How good are the McDonald criteria for childhood MS? D. Pohl. Department of Paediatrics and Paediatric Neurology, Georg-August-University, Robert-Koch-Strasse 40, 37075, Gottingen, Germany ¨ Since there is no simple test to secure the diagnosis of multiple sclerosis (MS), diagnostic criteria have been created including a combination of clinical and paraclinical studies. Whereas the old Poser-criteria required evidence of two clinical disease attacks for the diagnosis of definite MS, the McDonald criteria of 2001 included paraclinical evidence of dissemination in time via MRI and principally enabled a diagnosis of MS as early as 3 months after a single attack. In 2005, a revision of the McDonald Criteria was created with the aim of speeding diagnosis. The minimum interval for paraclinical dissemination in time was defined even shorter, enabling a diagnosis of MS if new T2 lesions develop later than one month after the beginning of a first attack. No definition of acute disseminated encephalomyelitis (ADEM) was included in the original McDonald criteria, and the revised McDonald criteria question the existence of ADEM as a separate entity from MS, thereby circumventing the diagnostic dilemma MS versus ADEM. The McDonald criteria state that they would best apply to individuals between 10 and 59 years of age, thus including juvenile MS and
excluding true childhood MS. ADEM is considered to be more prevalent in children than in adults, and is a major differential diagnosis of pediatric MS. The crucial question with regard to the applicability of the (revised) McDonald criteria is thus whether they allow a reliable diagnosis of pediatric MS, or if the rather liberal definition of dissemination in time might lead to the false diagnosis of MS in children with ADEM. This issue has to be urgently addressed, but until definite disease markers will be identified, only prospective longitudinal studies over periods as long as possible, ideally at least a decade, will be able to conclusively determine the validity of the McDonald criteria for pediatric MS. INV29 Treatment of childhood multiple sclerosis B. Anlar. Hacettepe University, Ankara, Turkey Treatment decisions in childhood MS are usually extrapolated from adult data. However several aspects of childhood MS differ considerably from adults, casting doubt on the validity of medical decisions. Diagnostic criteria and natural course of the disorder have not been validated in children. Therefore, disease-modifying therapies aiming at ameliorating the course of MS in childhood need to be justified. Acute demyelinating attacks are treated with glucocorticoids which hasten clinical recovery and resolution of gadoliniumpositive MRI lesions. Because abrupt discontinuation can result in relapses, oral taper over weeks is recommended as in acute disseminated encephalomyelitis. Attacks with sensory symptoms only, or those recovering already need no specific treatment. Disease-modifying therapies: Beta Interferons and Glatiramer acetate have been used in children. However they are not marketed and their doses are not defined for children. A reduced rate of relapses during follow-up of 2−3 years have been reported to date. Currently the limited nature of the data vs. the possibly higher efficacy of these drugs when used early appear to distance the clinician from evidence-based medicine.
10.30−12.00 Epilepsy preventive measures INV30 First epileptic seizure: to treat or not to treat? A. Covanis. Neurology Department, Agia Sophia Children’s Hospital, Athens, Greece Epileptic seizures are symptoms that occur in acute illness (provoked seizures linked to a specific trigger) or in epilepsy (unprovoked seizures with no obvious precipitating factor) and result from hyperexcitability, that is an imbalance between excitatory and inhibitory activity, of the cerebral neurons. Provoked seizures may be caused by, for example, metabolic disorders, febrile state, head trauma, stroke, drugs and alcohol withdrawal, which if present, preclude the diagnosis of an unprovoked episode. Furthermore, a variety of different paroxysmal events can in childhood be provoked by anger, frustration, stress, sleep deprivation or sleep, arousal, standing, bathing, menstruation, hyperventilation, chronic fatigue, alcohol, the use of illicit drugs in adolescence and are easily confused with seizures. In childhood all type of epileptic seizures are seen: epileptic spasms, typical and atypical absences, tonic, atonic, myoclonic and tonic clonic seizures and focal seizures. Some seizures are specific in childhood such as rolandic, autonomic, childhood absence seizures, tonic, atonic, astatic. The epileptic seizures, convulsive and non-convulsive, are generalised where the whole cerebral cortex or brain is involved and focal where