Current Problems in Diagnostic Radiology
Volume 41, Issue 1 , Pages 11-19, January 2012

Neuroimaging of Migrational Disorders in Pediatric Epilepsy

  • M. Reza Taheri, MD, PhD

      Affiliations

    • Department of Radiology, The George Washington University Hospital, Washington, DC
    • Corresponding Author InformationReprint requests: M. Reza Taheri, 900 23rd Street, NW, Ground Floor, Suite 2092, Room 126, Washington, DC 20037
    • ,
  • Andres Krauthamer, MD

      Affiliations

    • Department of Radiology, The George Washington University Hospital, Washington, DC
    • ,
  • Jeff Otjen, MD

      Affiliations

    • Department of Radiology, Seattle Children's Hospital, Seattle, WA
    • ,
  • Paritosh C. Khanna, MD

      Affiliations

    • Department of Radiology, Seattle Children's Hospital, Seattle, WA
    • ,
  • Gisele E. Ishak, MD

      Affiliations

    • Department of Radiology, Seattle Children's Hospital, Seattle, WA

Article Outline

Seizures in children are common and represent a final pathway for a variety of brain insults. Although most children with seizures do not require imaging, when indicated, imaging plays an important role in the clinical workup. Imaging in the pediatric seizure population is reserved for a particular subset of patients depending on factors, such as age of onset, symptomatology, physical examination findings, and specific electroencephalography changes to name a few. The etiologies of seizures are extensive and include disorders of cortical migration and organization. Cortical migration and organization disorders are multifactorial and complex and a major cause of seizure disorders. Although magnetic resonance imaging is the most common imaging modality used to identify the seizure focus, positron emission tomographic and/or diffusion tensor imaging are beginning to provide complementary information about the involved areas. Early and accurate detection is key to better treatment and overall improved patient prognosis.

 

Approximately 30,000 new cases of pediatric epilepsy are reported each year.1 Seizures in children represent a final pathway for a variety of brain insults. The etiologies for seizures are extensive, including traumatic, infectious, neoplastic, vascular, congenital, autoimmune, and metabolic conditions.

Imaging is reserved for afebrile patients with unexplained cognitive or motor impairment, abnormal neurological examination, seizure of focal onset, electroencephalography changes other than primary partial or primary generalized epilepsy, or for those who are less than 1 year old.1, 2 In patients with refractory epilepsy, neuroimaging is crucial for precisely identifying epileptogenic foci that are potentially amenable to surgical resection. Advances in multimodality neuroimaging with magnetic resonance (MR) imaging, diffusion tensor imaging, MR images fused with fluorine 18 fluorodeoxyglucose (FDG) positron emission tomographic (PET) images, and magnetic source imaging play an essential role in noninvasively localizing seizure onset zones in presurgical assessment.2, 3

Disorders of cortical migration and organization are a major cause of seizure disorders that are often difficult to manage.3, 4 Causes are multifactorial as neuronal migration is controlled by a complex interaction of neurons, signaling molecules, and anatomic structures. Other common clinical findings include developmental delay, hypotonia, microcephaly, and failure to thrive. Diagnoses in this group include lissencephaly, schizencephaly, pachygyria, polymicrogyria, agyria, heterotopias, and others.4, 5 Early and accurate detection is key to better treatment and patient outcome.

The goal of this pictorial essay is to review the role of imaging in the clinical workup of children with seizures and to depict radiologically detectable migrational and cortical arrangement disorders, which result in seizures.

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Imaging Techniques 

Proper imaging of children with seizures can improve both detection of an underlying etiology and patient safety. A unique challenge encountered in the imaging of pediatric epilepsy is the inability of children to cooperate for the long image acquisition times. Motion artifact may significantly impede the detection of subtle abnormalities associated with pediatric epilepsy. Ideally, this limitation is addressed with audio-video distraction and child-friendly settings. However, in some instances, sedation is required.3, 6

The use of a 3-Tesla magnet should be considered in those suspected of having focal cortical dysplasia. Detection of other lesions, including mesial temporal sclerosis, is relatively independent of the strength of the magnet. A patient's study should begin with a T1-weighted spoiled gradient recalled pulse sequence. The radiologist should review axial, coronal, and sagittal spoiled gradient recalled pulse sequences while other routine sequences, such as T2 and fluid-attenuated inversion recovery, are being obtained. Contrast should only be administered in those cases in which administration of contrast can further delineate the pathology detected on the noncontrast images, such as a tumor.

In patients whose seizures are refractory to medical treatment, neuroimaging is essential for precisely identifying epileptogenic foci that are potentially amenable to surgical resection for possible cure. Not all causes of pediatric epilepsy are detectable with conventional MR imaging. Advances in neuroimaging have recently improved lesion detection and localization. When the epileptogenic substrate is not identified, further evaluation with diffusion tensor imaging, MR-FDG-PET fusion images, and magnetic source imaging may be performed for improved lesion detection and localization.3, 5

Diffusion tensor imaging is an MR imaging technique that is in its early stages of development when applied to epilepsy imaging. It makes use of the anisotropic water diffusion properties in cerebral white matter to delineate microstructural tissue organization and the abnormal changes that take place in epilepsy.7 MR-FDG-PET fusion imaging allows direct correlation of anatomic abnormalities detected on MR imaging with the metabolic abnormalities detected on FDG-PET imaging. Fusion imaging takes advantage of the differences in abnormal neuronal metabolic activity in both the ictal and the interictal states. In the ictal state, areas of abnormal activity are seen as foci of hypermetabolic activity, whereas in the interictal state, they are seen as hypometabolic foci.8, 9 Magnetic source imaging is derived from the coregistration of spatially localized data from a magnetoencephalogram with the anatomic data from MR imaging. This allows for more precise localization of epileptogenic activity than with a conventional electroencephalography.10, 11 As with MR-FDG-PET fusion imaging, magnetic source imaging allows the detection of subtle abnormalities that may otherwise go undetected with conventional MR imaging (Fig 1).

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  • FIG 1. 

    (A) An axial T2 weighted MRI of the brain of an 8 year old patient shows a subtle focus of cortical thickening in the inferior right frontal lobe, suggestive of focal cortical dysplasia (arrow). (B) A fused PET-MRI shows mild decreased radiotracer uptake in the right inferior temporal lobe, right operculum and right inferior frontal region (arrows). (Color version of figure is available online.)

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Gray Matter Heterotopia 

These patients often present with seizures in infancy. Milder forms can be asymptomatic and found incidentally. Imaging shows a regional (Fig 2) or focal (Fig 3) parenchymal abnormality that follows gray matter on all MR pulse sequences but is abnormal in location, but usually within the white matter, along glial migration pathways (subependymal and within lobar white matter). This can be nodular or mass-like, focal or multifocal, or band-like.6, 7 Prognosis depends on extent of disease and ability to control symptoms. Initial management is medical, but surgical options are often pursued. To facilitate surgical treatment, it is important to ensure that the contralateral hemisphere is normal.

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  • FIG 2. 

    Regional gray matter heterotopias: T1-weighted image show extensive nodular areas with signal intensity similar to gray matter in the periventricular white matter (brackets). (Color version of figure is available online.)

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  • FIG 3. 

    Focal gray matter heterotopias. Coronal T1 (A) and T2 (B) images showing a focal nodular area with signal similar to gray matter in the left frontal periventricular white matter (arrow). (Color version of figure is available online.)

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Focal Cortical Dysplasia 

Focal cortical dysplasia (FCD) is recognized as 1 of the most common causes of intractable seizures in 0- to 3-year-old patients and accounts for nearly 80% of all surgically treated cases in children under the age of 3.12, 13 FCD was first described in 1971 as a distinct subtype of malformation of cortical development (MCD).13, 14 Unlike other MCDs, such as pachygyria, polymicrogyria, and hemimegalencephaly, FCD is not associated with diffuse abnormal gyration, but rather with subtle focal changes that at times can only be appreciated microscopically.14, 15 FCDs can be located in any part of the cortex, vary in size, and may affect multiple lobes. An ad hoc Task Force of the International League Against Epilepsy (ILAE) Diagnostic Methods Commission recently proposed an international consensus classification system for the histopathological classification of FCD.15, 16 As demonstrated in Table 1, the ILAE Task Force has proposed a 3-tiered classification system distinguishing isolated forms of type I and type II FCDs from FCD type III, which occurs in combination with another principal lesion (Table 1). Unless the area of FCD is large, patients do not have severe neurologic deficits and the main clinical manifestation is epilepsy. However, affected individuals can also exhibit behavioral disturbances, especially those with early onset epilepsy.15, 17

TABLE 1. The 3-tiered ILAE Diagnostic Methods Commission histologic classification system of FCD
Type of focal cortical dysplasiaHistologic features
Type I(a)FCD with abnormal radial cortical lamination
Type I(b)FCD with abnormal tangential cortical lamination
Type I(c)FCD with abnormal radial and tangential cortical lamination
Type II(a)FCD with dysmorphic neurons
Type II(b)FCD with dysmorphic neurons and balloon cells
Type III(a)Cortical lamination abnormalities in the temporal lobe associated with hippocampal sclerosis
Type III(b)Cortical lamination abnormalities adjacent to a glial or glioneuronal tumor
Type III(c)Cortical lamination abnormalities adjacent to vascular malformation
Type IIIrdCortical lamination abnormalities adjacent to any other lesion acquired during early life, eg, trauma, ischemic injury, encephalitis

FCD, focal cortical dysplasia.

Classical imaging findings for type II focal cortical dysplasia are a focal area of blurring of the gray-white matter junction, often with some increased fluid-attenuated inversion recovery signal and increased cortical thickness. Findings often taper toward the ventricle with a predilection for the frontal lobe (Fig 4). Type I focal cortical dysplasia can be difficult to detect with magnetic resonance imaging (MRI), as the only clue may be a subtle focus of T2 signal hyperintensity in the subcortical white matter, typically in the temporal lobe. FDG-PET-MRI has been shown to improve detection of such lesions.3, 18 Associated gyration or sulcal pattern abnormality and blurring of the gray-white junction can be present for either type I or II.16, 19 Currently subtypes of type I and II cannot be radiographically distinguished.17, 20 Surgical intervention is common considering that associated seizures are often refractory to medical management.

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  • FIG 4. 

    Focal cortical dysplasia. (A) Postcontrast axial T1 image shows a subtle area of nonenhancing low signal extending from the left frontal gray matter into the periventricular white matter (arrow). (B) Focal cortical dysplasia. Axial T2 image showing high signal extending from the left frontal cortex into the periventricular white matter (arrow), typical for type II focal cortical dysplasia (arrow). (Color version of figure is available online.)

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Polymicrogyria and Pachygyria 

This disorder varies in age of presentation and severity based on extent of the disease. Polymicrogyria implies abnormally numerous, small gyri in a focal, regional (lobar), or diffuse (hemispheric) distribution. Pachygyria by contrast implies thick gyri. The 2 terms are often used in conjunction since on lower resolution imaging, the multiple small gyri can look like a single thick gyrus and it may be difficult to separate 1 condition from the other. As more imaging resolution becomes available to depict smaller and smaller microgyri, the 2 disorders can be better distinguished. Abnormality is often most prominent at the sylvian fissure or in a perisylvian location (FIG 5, FIG 6).10, 21 Management can be surgical or medical.

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  • FIG 5. 

    Polymicrogyria. Sagittal T1 image shows the insular cortex is composed of small irregular appearing gyri (arrow). (A) This subtle finding is better appreciated when compared to the contralateral normal side (arrow) (B). (Color version of figure is available online.)

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  • FIG 6. 

    Polymicrogyria. Axial T1 image shows the right insular and adjacent cortex is composed of numerous small irregular gyri (arrow). (Color version of figure is available online.)

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Schizencephaly 

The key finding for schizencephaly is a unilateral or bilateral cerebral cleft lined with abnormal, dysplastic gray matter. It results from either genetic or acquired causes and occurs early in fetal development with the disruption of migration of germinal matrix cells from the subependyma, and their failure to form normal cortical gray matter. The presence of dysplastic, polymicrogyric gray matter lining the cleft distinguishes schizencephaly from other cerebrospinal fluid clefts, such as porencephalic cysts. In type I (closed lip) schizencephaly, gray matter lining each side of the cleft is in direct apposition. The cleft runs from the pial surface of the cortex to the ependymal surface of the lateral ventricle, where a focus of “beaking” along the ventricular margin usually suggests contiguity with the ventricle (Fig 7). In type II (open lip) schizencephaly, a cerebrospinal fluid space is visible (Fig 8). Type II is more common and symptomatically more severe.18, 22 Schizencephaly may be associated with absent septum pellucidum19, 23 and septo-optic dysplasia, particularly in cases of bilateral open lip schizencephaly.

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  • FIG 7. 

    Type I Schizencephaly (closed lip). Axial T2 (A) and T1 (B) weighted images show a subtle beaking of the ventricle (arrow). There is heterotopic grey matter lining the ventricle and extending from the ventricle to the surface of the brain. (Color version of figure is available online.)

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  • FIG 8. 

    Schizencephaly Type II (open lip). Axial T2 image shows grey matter-lined parenchymal cleft extending from right lateral ventricle to the subarachnoid space (arrow). (Color version of figure is available online.)

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Lissencephaly 

Lissencephaly is characterized by a thick cortex and an incompletely formed gyri (incomplete lissencephaly or pachygyria) or absent gyri (complete lissencephaly or agyria), resulting in a smooth appearance of the surface of the brain, classically with an “hour-glass” configuration on coronal images, with bilateral “narrowing” at the smooth sylvian fissures (Fig 9). There can be associated band-heterotopias that underlie the refractory seizures. The thicker the band, the thinner the cortical mantle and more severe the seizures. It can occur as an isolated defect (classic lissencephaly) or in association with an underlying syndrome, such as Miller-Dieker syndrome or Norman-Roberts syndrome.20, 24 Lissencephaly has been associated with several genetic abnormalities, both autosomal and X-linked. Prognosis is generally poor but varies with the degree of abnormal gyration.

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  • FIG 9. 

    Lissencephaly. Axial (A) and coronal (B) T2 images show diffuse lack of gyrations throughout the cortex and a smooth contour to the cerebrum in this full-term neonate. Thick diffuse band heterotopia is present (arrows). (Color version of figure is available online.)

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Hemimegalencephaly 

Enlargement of a unilateral cerebral hemisphere or hemimegalencephaly is defined as overgrowth of a part or all of a cerebral hemisphere, which is a manifestation of a more complex defect, including abnormal neuronal proliferation, migration, and organization (Fig 10). Although the occipital lobe is most commonly involved, any lobe may be affected. It can be isolated or associated with hemihypertrophy syndromes, such as Proteus syndrome or epidermal nevus syndrome. Imaging findings are variable but typically include enlargement of the ipsilateral ventricle and often show associated abnormalities of cortical development, such as polymicrogyria, focal dysplasia, or heterotopia. Patients will often have worsening and intractable seizures, which can eventually affect the normal hemisphere. Treatment is initially medical; however, it often progresses to surgery with hemispherectomy being the procedure of choice. Close evaluation of the less affected hemisphere is essential, as an abnormality on this side can be a contraindication for surgery.

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  • FIG 10. 

    Hemimegalencephaly. Axial T1 (A) and T2 (B) images show diffuse abnormal enlargement of the right cerebral hemisphere, with corresponding asymmetry of the skull. In this case, there are no focal areas of abnormal cortical development.

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TORCH Infections 

TORCH infections, particularly cytomegalovirus infection, can cause migration abnormalities in as many as 10% of patients.25, 26 Because neurons form between 8 and 20 weeks of gestation, the hallmark of early cytomegalovirus infection is a loss of neurons and glial cells.21, 27 Second-trimester infections are characterized by migration abnormalities, such as lissencephaly, pachygyria, cerebellar hypoplasia, diffuse focal polymicrogyria, and less commonly, schizencephaly. These migration abnormalities are often noted along with ventriculomegaly,25, 26 thick, chunky periventricular calcification, and focal, patchy, or confluent white matter abnormalities25, 26 (Fig 11).

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  • FIG 11. 

    Congenital cytomegalovirus. (A) Coronal computed tomography shows ventriculomegaly, extensive coarse calcifications lining the walls of the lateral ventricles, and abnormal hypodensity in the periventricular white matter. (B) Coronal T2-weighted MRI better illustrates the abnormally thin parenchyma with ventriculomegaly. Gradient recalled echo images (not shown) depicted all the periventricular chunky calcifications as low-signal areas.

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Conclusions 

Cortical migration and organization disorders are a common and multifactorial etiology of seizures in the pediatric patient population. Neuroimaging, whether with computed tomography imaging, MR imaging, MR-FDG-PET fusion imaging, magnetic source imaging, or diffusion tensor imaging, plays a critical role in the clinical workup of these disorders. Familiarity with the different imaging findings discussed throughout this pictorial review is vital for accurate diagnosis. Early recognition and treatment, regardless of the underlying cause of seizure, is vital for effective treatment and improved patient care.

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References 

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PII: S0363-0188(11)00051-X

doi:10.1067/j.cpradiol.2011.06.003

Current Problems in Diagnostic Radiology
Volume 41, Issue 1 , Pages 11-19, January 2012

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