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Neuroradiological assessment of brain structure and function and its implication in the pathogenesis of West syndrome

  • Csaba Juhász
    Affiliations
    Department of Pediatrics, Children's Hospital of Michigan, The Detroit Medical Center, Wayne State University School of Medicine, Detroit, MI, USA
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  • Harry T. Chugani
    Correspondence
    Corresponding author. Children's Hospital of Michigan, Pediatric Neurology/PET Center, 3901 Beaubien Boulevard, Detroit, MI 48201, USA. Tel.: +1-313-993-2867; fax: +1-313-993-3845
    Affiliations
    Department of Pediatrics, Children's Hospital of Michigan, The Detroit Medical Center, Wayne State University School of Medicine, Detroit, MI, USA

    Department of Neurology, Children's Hospital of Michigan, The Detroit Medical Center, Wayne State University School of Medicine, Detroit, MI, USA

    Department of Radiology, Children's Hospital of Michigan, The Detroit Medical Center, Wayne State University School of Medicine, Detroit, MI, USA
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  • Otto Muzik
    Affiliations
    Department of Pediatrics, Children's Hospital of Michigan, The Detroit Medical Center, Wayne State University School of Medicine, Detroit, MI, USA

    Department of Radiology, Children's Hospital of Michigan, The Detroit Medical Center, Wayne State University School of Medicine, Detroit, MI, USA
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  • Diane C. Chugani
    Affiliations
    Department of Pediatrics, Children's Hospital of Michigan, The Detroit Medical Center, Wayne State University School of Medicine, Detroit, MI, USA

    Department of Radiology, Children's Hospital of Michigan, The Detroit Medical Center, Wayne State University School of Medicine, Detroit, MI, USA
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      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.

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