Abstract
Neuroimaging studies with magnetic resonance imaging (MRI) and positron emission tomography
(PET) scanning have contributed significantly to our understanding of West syndrome.
Cortical dysplastic lesions are the most common abnormalities seen with MRI in infants
with spasms, but other structural lesions are also detected occasionally. An underlying
cortical dysplasia may not be apparent until myelination has advanced in the brain
and poor gray–white matter differentiation becomes observable. Many cortical dysplastic
lesions can only be detected using PET scanning of glucose metabolism or γ-aminobutyric
acidA (GABAA) receptor binding. The MRI and PET findings, together with neurophysiological observations,
strongly suggest that infantile spasms are initiated as cortical epileptic discharges
that, during a ‘critical’ developmental period, may undergo secondary generalization
in an age-dependent mechanism to emerge as spasms. The onset of spasms often coincides
with the functional maturation of cerebral cortex. Based on data from glucose metabolism
PET scanning as well as electrophysiological and neurochemical findings on infants
with spasms, we have postulated that the offending lesion is a focal or diffuse cortical
abnormality which, at a critical stage of maturation, causes abnormal functional interactions
with brainstem raphe nuclei which project widely throughout the brain. Raphe-cortical
projections could mediate the hypsarrhythmic changes seen on EEG. The prominent serotonergic
raphe-striatal pathway and descending spinal pathways may be responsible for secondary
generalization of the cortical discharges to result in the relatively symmetric spasms.
It is likely that additional factors (e.g. genetic) play a role in the manifestation
of the age-specific electroclinical features of West syndrome. Recently developed
PET tracers can be used to detect epileptogenic brain regions and also to investigate
developmental abnormalities of serotonergic (using the tracer α[11C]methyl-l-tryptophan) and GABAergic (using [11C]flumazenil) neurotransmitter systems. These systems are implicated in epileptogenesis,
and their involvement in the pathophysiology of West syndrome can be further addressed
by future functional neuroimaging studies.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Brain and DevelopmentAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Clinical and electroencephalographic classification of epileptic seizures.Epilepsia. 1970; 11: 102-112
- Value of magnetic resonance imaging in West syndrome of unknown etiology.Epilepsia. 1993; 34: 701-706
- Magnetic resonance imaging in developmental disorders of the cerebral cortex.Epilepsia. 1994; 35: S44-S56
- Cellular and molecular basis of cerebral dysgenesis.J Neurosci Res. 1997; 50: 907-916
- Microscopic cortical dysplasia in infantile spasms: evolution of white matter abnormalities.Am J Neuroradiol. 1995; 16: 1265-1272
- West syndrome: etiological and prognostic aspects.Brain Dev. 1998; 20: 1-8
- Etiologic classification of infantile spasms in 140 cases: role of positron emission tomography.J Child Neurol. 1996; 11: 44-48
- MR in partial epilepsy: value of high-resolution volumetric techniques.Am J Neuroradiol. 1995; 16: 339-343
- Prospective magnetic resonance imaging identification of focal cortical dysplasia, including the non-balloon cell subtype.Ann Neurol. 1998; 44: 749-757
- Diagnosis of subtle focal dysplastic lesions: curvilinear reformatting from three-dimensional magnetic resonance imaging.Ann Neurol. 1999; 46: 88-94
- MRI texture analysis improves detection of focal cortical dysplasia (abstract).Epilepsia. 2000; 41: 82-83
- Diffusion tensor imaging in patients with epilepsy and malformations of cortical development.Brain. 2001; 124: 617-626
- Positron emission tomography.in: Engel Jr., J. Pedley T.A. Epilepsy: a comprehensive textbook. Lippincott-Raven, Philadelphia, PA1997: 947-968
- Is epileptogenic cortex truly hypometabolic on interictal positron emission tomography?.Ann Neurol. 2000; 48: 88-96
- Preoperative and postoperative glucose consumption in mesiobasal and lateral temporal lobe epilepsy.Neurology. 1994; 44: 2125-2132
- In vivo cerebral metabolism and central benzodiazepine-receptor binding in temporal lobe epilepsy.Neurology. 1993; 43: 1998-2006
- Glucose and [11C]flumazenil PET abnormalities of thalamic nuclei in temporal lobe epilepsy.Neurology. 1999; 53: 2037-2045
- Ictal patterns of cerebral glucose utilization in children with epilepsy.Epilepsia. 1994; 35: 813-822
- Basic mechanisms of childhood epilepsies: studies with positron emission tomography.Adv Neurol. 1999; 79: 883-891
- Subcortical structures and pathways involved in convulsive seizure generation.J Clin Neurophysiol. 1992; 9: 264-277
- Infantile spasms: I. PET identifies focal cortical dysgenesis in cryptogenic cases for surgical treatment.Ann Neurol. 1990; 27: 406-413
- Surgery for intractable infantile spasms: neuroimaging perspectives.Epilepsia. 1993; 34: 764-771
- Epileptic syndromes and cerebral malformations in infancy: multicenter study.Boll Lega Ital Epil. 1984; 45/46: 65-67
- Facilitation of infantile spasms by partial seizures.Epilepsia. 1993; 34: 97-109
- Maturational changes in cerebral function in infants determined by 18FDG positron emission tomography.Science. 1986; 231: 840-843
- Positron emission tomography study of human brain functional development.Ann Neurol. 1987; 22: 487-497
- Localization of focal cortical lesions influences age of onset of infantile spasms.Epilepsia. 1996; 37: 1068-1071
- Infantile spasms: III. Prognostic implications of bitemporal hypometabolism on positron emission tomography.Ann Neurol. 1996; 39: 643-649
- Prenatal etiologies of West syndrome.Epilepsia. 1993; 34: 716-722
- Infantile spasms: II. Lenticular nuclei and brain stem activation on positron emission tomography.Ann Neurol. 1992; 31: 212-219
- The serotoninergic innervation of cerebral cortex: different classes of axon terminals arise from dorsal and median raphe nuclei.Synapse. 1987; 1: 153-168
- CNS connections with the median raphe nucleus: retrograde tracing with WGA-apoHRP-Gold complex in the rat.J Comp Neurol. 1989; 289: 11-35
- Awakening the sleeping giant: anatomy and plasticity of the brain serotonergic system.J Clin Psychiatry. 1991; 52: 4-16
- Organization of the ascending striatal afferents in monkeys.J Comp Neurol. 1980; 189: 307-321
- High affinity serotonin binding sites in human brain: a comparison of cerebral cortex and basal ganglia.J Neural Transm. 1989; 76: 211-219
- Ontogeny and topography of seizure regulation by the substantia nigra.Brain Dev. 1995; 17: 61-72
- What is GABAergic inhibition? How is it modified in epilepsy?.Epilepsia. 2000; 41: S90-S95
- Epilepsy-associated plasticity in gamma-aminobutyric acid receptor expression, function, and inhibitory synaptic properties.Int Rev Neurobiol. 2001; 45: 237-252
- Cerebrospinal fluid GABA levels in children with infantile spasms.Neurology. 1984; 34: 235-238
- Putative neurotransmitter abnormalities in infantile spasms: cerebrospinal fluid neurochemistry and drug effects.J Child Neurol. 1994; 9: 119-129
- Developmental profile of GABAA-receptors in the marmoset monkey: expression of distinct subtypes in pre- and postnatal brain.J Comp Neurol. 1996; 367: 413-430
- Temporal modulation of GABA(A) receptor subunit gene expression in developing monkey cerebral cortex.Neuroscience. 1999; 91: 1223-1245
- Postnatal maturation of human GABAA receptors measured with positron emission tomography.Ann Neurol. 2001; 49: 618-626
- Excitatory GABA responses in embryonic and neonatal cortical slices demonstrated by gramicidin perforated-patch recordings and calcium imaging.J Neurosci. 1996; 16: 6414-6423
- The GABA paradox: multiple roles as metabolite, neurotransmitter, and neurodifferentiative agent.J Neurochem. 1999; 73: 1335-1342
- Cortical benzodiazepine receptor changes are related to frequency of partial seizures: a positron emission tomography study.Epilepsia. 1996; 37: 236-244
- Intracranial EEG versus flumazenil and glucose PET in children with extratemporal lobe epilepsy.Neurology. 2000; 54: 171-179
- Relationship of flumazenil and glucose PET abnormalities to neocortical epilepsy surgery outcome.Neurology. 2001; 56: 1650-1658
- Cerebrospinal fluid monoamine metabolites in patients with infantile spasms.Neurology. 1984; 34: 102-105
- Changes in CSF neurotransmitters in infantile spasms.Pediatr Neurol. 1991; 7: 440-445
- Studies on CSF tryptophan metabolism in infantile spasms.Pediatr Neurol. 1991; 17: 411-414
- Infantile spasms associated with 5-hydroxytryptophan administration in patients with Down's syndrome.Neurology. 1971; 21: 911-919
- The serotonergic innervation of the cerebral cortex in man and its changes in focal cortical dysplasia.Epilepsy Res. 1996; 25: 79-106
- Levels of biogenic amines, their metabolites, and tyrosine hydroxylase activity in the human epileptic temporal cortex.Synapse. 1990; 5: 152-156
- α-Methyl tryptophan as a tracer for in vivo studies of brain serotonin system, from autoradiography to positron emission tomography.J Chem Neuroanat. 1992; 5: 349-354
- Analysis of [C-11]alpha-methyl-tryptophan kinetics for the estimation of serotonin synthesis rate in vivo.J Cereb Blood Flow Metab. 1997; 17: 659-669
- Imaging epileptogenic tubers in children with tuberous sclerosis complex using alpha-[11C]methyl-l-tryptophan positron emission tomography.Ann Neurol. 1998; 44: 858-866
- Evidence that [11C]methyl-l-tryptophan PET traces tryptophan metabolism via the kynurenine pathway in tuberous sclerosis complex (abstract).Soc Neurosci Abstr. 1998; 24: 1757
- Alpha[C-11]methyl-l-tryptophan PET maps brain serotonin synthesis and kynurenine pathway metabolism.J Cereb Blood Flow Metab. 2000; 20: 2-9
- Convulsant action of intracerebroventricularly administered l-kynurenine sulphate, quinolinic acid and other derivatives of succinic acid, and effects of amino acids: structure-activity relationships.Neuropharmacology. 1982; 21: 1227-1233
- An iontophoretic investigation of the actions of convulsant kynurenines and their interaction with the endogenous excitant quinolinic acid.Brain Res. 1982; 247: 184-187
- Neuroactive amino acids in focally epileptic human brain: a review.Neurochem Res. 1999; 24: 1387-1395
- Evidence for coupling between glucose metabolism and glutamate cycling using FDG PET and 1H magnetic resonance spectroscopy in patients with epilepsy.J Cereb Blood Flow Metab. 2000; 20: 871-878
- Postnatal development of monoamine content and synthesis in the cerebral cortex of rhesus monkeys.Brain Res. 1982; 256: 339-349
- Synchronized overproduction of neurotransmitter receptors in diverse regions of the primate cerebral cortex.Proc Natl Acad Sci USA. 1991; 88: 10218-10221
- Developmental changes in brain serotonin synthesis capacity in autistic and nonautistic children.Ann Neurol. 1999; 45: 287-295
- Experimental models of epilepsy in young animals.J Child Neurol. 1994; 9: S3-S11
- Age-specific N-methyl-d-aspartate-induced seizures: perspectives for the West syndrome model.Epilepsia. 1999; 40: 1357-1369
Article info
Publication history
Accepted:
June 14,
2001
Received in revised form:
June 11,
2001
Received:
May 28,
2001
Identification
Copyright
© 2001 Elsevier Science B.V. Published by Elsevier Inc. All rights reserved.
