1. Deconvoluting convulsions: An MRI-based review of pediatric epilepsy (eEdE-177)
Fang Yu M.D.1, Yun Xie M.D.1, Michael Wang M.D.1, Girish Bathla M.D.2, Wilson Altmeyer M.D.1, Achint Singh M.D.1
1University of Texas Health Science Center in San Antonio
2Mallinckrodt Institute of Radiology

2. Disclosures
The authors have no disclosures

3. Table of contents Back Next Introduction Imaging Considerations
Mesial Temporal Sclerosis
Neoplasms
Congenital Abnormalities
Neurocutaneous Syndromes

4. Back
Next
Home
Introduction
Approximately 25% of children with epilepsy have a form that is unresponsive to medical therapy [1].
In up to 80% of medically refractory epilepsy cases, an underlying structural abnormality is detected on imaging [2].
These have important implications on treatment [3].
Broadly, these include:
Neoplasms
Developmental anomalies
Gliosis
Neurocutaneous syndromes
1. Trichard M, Léautaud A, Bednarek N, Mac-Caby G, Cardini-Poirier S, Motte J, Hoeffel C. Neuroimaging in pediatric epilepsy. 5, May 2012, Arch Pediatr, Vol. 19, pp
2. CP, Panayiotopoulos. The Epilepsies: Seizures, Syndromes and Management. Oxfordshire : Bladon Medical Publishing, 2005.
3. Jung da E, Lee JS. Multimodal neuroimaging in presurgical evaluation of childhood epilepsy. 8, August 2010, Korean J Pediatr, Vol. 53, pp

5. Imaging Considerations
Back
Next
Home
Imaging Considerations
Special considerations in pediatric subjects include difficulty with cooperation for lengthy exams.
This may be addressed with either audio-visual aids for distraction or the use of general anesthesia [4].
The following protocol should be included for thorough evaluation of a patient with medically refractory epilepsy:
3D T1-weighted sequence (i.e. MPRAGE [Magnetization-Prepared Rapid Acquisition Gradient Echo])
Increased SNR, allows improved detection of cortical abnormalities and lesions at the grey-white junction.
4. Rastogi S, Lee C, Salamon N. “Neuroimaging in pediatric epilepsy: a multimodality approach.” Radiographics. 2008 Jul-Aug;28(4):

6. Imaging Considerations
Back
Next
Home
Imaging Considerations
High resolution axial & coronal T2 weighted and FLAIR sequences
Helps in evaluation of the hippocampi, as well as other lesions.
T2* or SWI (susceptibility weighted imaging)
The detection of blood products (i.e. ferritin) as well as calcifications can aid in the differential.
T1-post gadolinium sequence
Helpful in the evaluation of tumors and vascular lesions.
Other advanced MR sequences, including DTI (diffusion tensor imaging), functional MRI, and MR Spectroscopy may be considered in specific situations.

7. Mesial Temporal Sclerosis
Back
Next
Home
Mesial Temporal Sclerosis
Mesial Temporal Sclerosis (MTS) is the most common cause of partial complex epilepsy.
There is often a second pathology noted (in up to 15% of cases), most often focal cortical dysplasia
It is thought that early insults to the hippocampus (e.g. complicated febrile seizures, trauma, infection) result in a hypoxic-ischemic injury [5] [6].
Most often affects the body of the hippocampus (up to 90%), followed by the tail & head [5].
CA1 & CA4 areas of Ammon Horn are most vulnerable
5. Osborn
6. Mathern GW, Babb TL, Vickrey BG, Melendez M, Pretorius JK. “The clinical-pathogenic mechanisms of hippocampal neuron loss and surgical outcomes in temporal lobe epilepsy”. Brain 1995; 118(pt 1): 105–118.

8. Mesial Temporal Sclerosis
Back
Next
Home
Mesial Temporal Sclerosis
MRI:
T1 weighted images demonstrate volume loss of the affected hippocampus.
Can often see atrophy of the ipsilateral fornix, and dilation of the temporal horn
T2/FLAIR images demonstrate hyperintensity of the affected hippocampus
Surgical removal of the abnormalities seen on MRI (usually anteromedial temporal lobectomy) leads to resolution of symptoms in 70-90% of cases [5].

9. Mesial Temporal Sclerosis
Back
Next
Home
Mesial Temporal Sclerosis a b c
Figure 1: High resolution coronal T2W (a) and FLAIR (b) images of the brain demonstrate asymmetric atrophy and hyperintensity involving the right hippocampus. On axial FLAIR image, there is apparent dilation of the ipsilateral anterior temporal horn.

10. Back
Next
Home
Neoplasms
Although any cerebral tumor can be associated with pediatric seizures, a few are characteristically associated.
These include lesions containing glial & neuronal elements: ganglioglioma, gangliocytoma, pleomorphic xanthoastrocytoma (PXA), and dysembryoplastic neuroepithelial tumor (DNET) [7].
Many authors include hypothalamic hamartomas in this group, although this is not a neoplasm.
The majority of these lesions occur in children or young adults, and have low malignant potential.
Blumcke I, Lobach M, Wolf HK, Wiestler OD. “Evidence for developmental precursor lesions in epilepsy-associated glioneuronal tumors”. Microsc Res Tech. 1999; 46:53–58.

11. Back
Next
Home
Neoplasms
Can be seen in association with focal cortical dysplasia, and there has been suggestion of a shared precursor [7].
Typically, on imaging, these lesions are well-demarcated, with little growth over time.
Most are relatively T1 hypointense, with T2 hyperintensity, and minimal edema.
Contrast enhancement is often present.
Osborn

12. Neoplasms - Ganglioglioma
Back
Next
Home
Neoplasms - Ganglioglioma
Gangliogliomas (WHO grade I) are the most common neoplasm associated with temporal lobe epilepsy.
Contains neoplastic glial cells and dysplastic ganglion cells.
Although they can occur throughout the CNS, the temporal lobe is the most frequent location [5].
On MR imaging, these are cortically based lesions, appearing as a cyst with a mural nodule.
Surgical resection is usually curative.
Osborn

13. Neoplasms - Ganglioglioma
Back
Next
Home
Neoplasms - Ganglioglioma
Figure 2: Axial T2, coronal T2W, & axial FLAIR images (a, b, & c) demonstrate a hyperintense cystic lesion in the left hippocampus. There is no restricted diffusion (d). Subtle enhancement is noted about the periphery (f) compared to the pre-contrast T1 axial image (e). a b c
Osborn d e f

14. Back
Next
Home
Neoplasms - DNET
Disembryoblastic neuroepithelial tumors (DNETs), along with gangliogliomas, are among the most common tumors associated with refractory epilepsy.
WHO grade I, cortically-based, and affect individuals younger than 20 years [5].
On gross pathology, the tumors have a viscous consistency, with nodular components.
Histologically characterized by specific glioneuronal element (SGNE)
Adjacent dysplastic cerebral cortex is seen in up to 80% of cases.
Osborn

15. Back
Next
Home
Neoplasms - DNET
Due to frequently associated cortical dysplasia, more extensive resections are advocated compared to gangliogliomas
MRI demonstrates a characteristic “bubbly” appearing lesion, which is markedly T2 hyperintense, often with a hyperintense rim [5].
Enhancement is minimal or absent.
Susceptibility-sensitive sequences often demonstrating blooming artifact
Osborn

16. Neoplasms - DNET Back Next Home a d b c
Figure 3: Axial T2 image demonstrates a cortically based, multicystic lesion situated within the left parietal lobe (a), without significant surrounding edema. There is no significant diffusion restriction (b). Axial T1 pre- (c) and post-contrast (d) images demonstrate minimal enhancement.

17. Congenital Abnormalities
Back
Next
Home
Congenital Abnormalities
These include malformations of cortical development (MCD) as well as other lesions, such as hypothalamic hamartomas.
MCDs are congenital malformations that result from abnormalities involving cerebral cortex development [8].
Seizures associated with MCDs are secondary to malposition of normal cortical neurons or abnormal cortical neurons.
Causes included genetic, ischemic, toxic or infectious insults during normal cortical development.
Accounts for ~25% to 40% of medication resistant pediatric epilepsy.
75% of patients with MCD have epilepsy.
Add hypothalamic hamartoma here as separate from MCD (and make this slide congenital abnormalities)

18. Congenital Abnormalities
Back
Next
Home
Congenital Abnormalities
MCDs can be divided into 3 broad types [8]
Abnormal neuronal proliferation
Focal cortical dysplasia (FCD II)
Hemimegalencephaly
Abnormal neuronal migration
Classical Lissencephaly
Grey matter heterotopia
Abnormal cortical organization
Polymicrogyria
Schizencephaly
Focal cortical dysplasia (FCD I)

19. Congenital Abnormalities - Hypothalamic Hamartoma
Back
Next
Home
Congenital Abnormalities - Hypothalamic Hamartoma
Often categorized as a neoplasm, this actually represents a non-neoplastic grey matter heterotopia.
Occurs due to anomalous neuronal migration [4].
Clinically presents with precocious puberty (75%), behavioral disturbances, & gelastic seizures (fits of laughter or crying) [5].
Most often located in the tuber cinereum, interposed between the infundibulum anteriorly & the mamillary bodies posteriorly.
May project into the suprasellar cistern or third ventricle
Classification is morphologic (pedunculated versus sessile).

20. Congenital Abnormalities - Hypothalamic Hamartoma
Back
Next
Home
Congenital Abnormalities - Hypothalamic Hamartoma
Varies in size from millimeters to centimeters & may have solid-cystic components [4].
MRI:
May present as a intra- or para-hypothalamic lesion.
Typically T1 isointense to mildly hypointense to grey matter
No significant contrast enhancement.
T2/FLAIR iso- to slightly hyperintense, depending on the proportion of neuronal/glial tissue.

21. Congenital Abnormalities – Hypothalamic Hamartoma
Back
Next
Home
Congenital Abnormalities – Hypothalamic Hamartoma a b c
Figure 4: Axial (a) T2-weighted image demonstrates a well-circumscribed mildly hyperintense lesion in the region of the tuber cinereum. The lesion is minimally hypointense on the T1 sagittal image (b) without any enhancement on sagittal T1-weighted post contrast image.

22. Congenital Abnormalities – Focal cortical dysplasia
Back
Next
Home
Congenital Abnormalities – Focal cortical dysplasia
Focal cortical dysplasia (FCD) involves subtle focal changes in gyration [8].
Most common cause of pediatric intractable epilepsy.
80% of all surgically treated causes in children under 3 years of age.
Divided into two subtypes based on histological findings:
Type I - milder form that may be asymptomatic
Type II - more associated with intractable epilepsy

23. Congenital Abnormalities – Focal cortical dysplasia
Back
Next
Home
Congenital Abnormalities – Focal cortical dysplasia
MR findings of FCD can be very subtle so a high level of suspicion is needed. Features include:
Subtle cortical/subcortical hyperintensity on T2/FLAIR
Often located at the bottom of a deep sulcus
Focal cortical thickening
Blur of grey/white matter junction
“Transmantle sign”
Hyper-intense FLAIR signal extending from the cortex to the margin of the ventricle, representing arrest of neuronal migration.

24. Congenital Abnormalities – Focal cortical dysplasia
Back
Next
Home
Congenital Abnormalities – Focal cortical dysplasia a b c
Figure 5: Axial T1 image demonstrates focal area of cortical thickening in the left parietal lobe (a). Axial FLAIR image demonstrates focal area of cortical/subcortical increased FLAIR signal intensity (b). Coronal FLAIR image demonstrates transmantle sign (c).

25. Congenital Abnormalities - Hemimegalencephaly
Back
Next
Home
Congenital Abnormalities - Hemimegalencephaly
A rare form of MCD that is characterized by hamartomatous growth of one cerebral hemisphere [8].
Presents with clinical triad of intractable partial seizure, hemiparesis and developmental delay
Can occur in isolation or in association with variety of syndromes, including neurofibromatosis-1, tuberous sclerosis, Epidermal Nevus syndrome and Klipple-Trenaunay-Weber syndrome

26. Congenital Abnormalities - Hemimegalencephaly
Back
Next
Home
Congenital Abnormalities - Hemimegalencephaly
The thickened cortex may have findings of lissencephaly, pachygyria or polymicrogyria
Treatment with early hemispherectomy is recommended.
MRI demonstrates:
Unilateral enlargement of cerebral hemisphere with cortical thickening
Ipsilateral enlargement of the lateral ventricle
Ipsilateral hypermyelination of the white matter

27. Congenital Abnormalities - Hemimegalencephaly
Back
Next
Home
Congenital Abnormalities - Hemimegalencephaly
T2W btw…
Also mention pachygyria a b
Figure 6: Axial (a) and coronal (b) T2 images demonstrate unilateral enlargement of the right cerebral hemisphere with ipsilateral enlargement of the right lateral ventricle, cortical thickening in the right temporal lobe, as well as subcortical heterotopic grey matter

28. Congenital Abnormalities – Band heterotopia
Back
Next
Home
Congenital Abnormalities – Band heterotopia
This conditions is also referred to as “double cortex”.
Characterized by a band of heterotopic gray matter situated between the lateral ventricular wall and the cortex.
Usually bilateral & symmetric.
May also be isolated to particular lobe(s) [5] [8].
Clinically presents with intellectual impairment and mixed seizure disorder.
There is a female predilection.

29. Congenital Abnormalities – Band heterotopia
Back
Next
Home
Congenital Abnormalities – Band heterotopia
Caused by mutations in DCX and LIS1 genes.
DCX gene is on the X chromosome [5] [8].
MRI demonstrates a “double cortex” with a band of symmetrical gray matter signal within the white matter, separated from the cerebral cortex by a layer of white matter.

30. Congenital Abnormalities – Band heterotopia
Back
Next
Home
Congenital Abnormalities – Band heterotopia a b c
Figure 7: Axial (a) & coronal (b) T1 and T2 coronal (c) images demonstrate symmetrical band of gray matter signal intensity within the white matter.

31. Congenital Abnormalities – Periventricular nodular heterotopia
Back
Next
Home
Congenital Abnormalities – Periventricular nodular heterotopia
Defined by findings of heterotopic gray matter foci, in this case being periventricular in location [5] [8].
May occur in isolation or in association with other developmental anomalies
80% to 90% of patients present with seizure symptoms
MRI demonstrates nodular foci of gray matter signal adjacent to the periventricular white matter that may protrude into the ventricular lumen.

32. Congenital Abnormalities – Periventricular nodular heterotopia
Back
Next
Home
Congenital Abnormalities – Periventricular nodular heterotopia a b c
Figure 8: T1 precontrast sagittal (a), axial (b), and coronal (c) images demonstrate nodular foci in a periventricular distribution that follows the gray matter signal intensity

33. Congenital Abnormalities - Polymicrogyria
Back
Next
Home
Congenital Abnormalities - Polymicrogyria
Defined as excessive microscopic gyration of the cerebral cortex [9].
Can occur as an isolated finding, or in conjunction with other abnormalities.
May occur diffusely or focally [10] [11].
The perisylvian cortex is most commonly involved.
60% to 85 % of patients will present with seizures, which usually begin at ages of 4 to 12 years.
MR imaging demonstrates numerous small gyri, with signal intensity matching that of the cortex.
Leventer RJ et al. Clinical and imaging heterogeneity of polymicrogyria: a study of 328 patients. Brain May;133(Pt 5):
Barkovich AJ. MRI analysis of sulcation morphology in polymicrogyria. Epilepsia 2010;51:17–22.
De Ciantis et al. Ultra-High-Field MR Imaging in Polymicrogyria and Epilepsy. AJNR 2015;36:309 –16

34. Congenital Abnormalities - Polymicrogyria
Back
Next
Home
Congenital Abnormalities - Polymicrogyria a b
Figure 9: Sagittal (a) and axial (b) T1 pre-contrast demonstrate excessive microscopic gyration involving the perisylvian cortices.

35. Congenital Abnormalities - Schizencephaly
Back
Next
Home
Congenital Abnormalities - Schizencephaly
True clefts in the cerebral hemispheres as result of failure of development of the cerebral mantle in the zone of cleavage [5].
The clefts are lined by abnormal gray matter (polymicrogyria).
Classified as open versus closed lip, with the former being characterized by separation of the cleft walls.
65% occur in the frontoparietal region, with the remaining 35% in the temporal or occipital lobes.
Present in 70% of agenesis of septum pellucidum cases.
Approximately 57% of cases present with seizure.
MRI demonstrates a cerebral cleft lined by gray matter.

36. Congenital Abnormalities - Schizencephaly
Back
Next
Home
Congenital Abnormalities - Schizencephaly a b
Figure 10: T2 axial (a) and coronal (b) images demonstrate a closed lipped schizencephaly involving the left frontal lobe lined by heterotopic grey matter.

37. Neurocutaneous Syndromes – Sturge-Weber Syndrome
Back
Next
Home
Neurocutaneous Syndromes – Sturge-Weber Syndrome
A rare neurocutaneous syndrome caused by extensive cortical pial angiomatous malformation
Characterized by clinically by seizures, progressive mental retardation, and facial telengiectatic nevi [5].
75% to 90% of patients present with epilepsy
Medication controls epilepsy in about 40% of the patients.
Surgical options include cortical excision to hemispherectomy.

38. Neurocutaneous Syndromes – Sturge-Weber Syndrome
Back
Next
Home
Neurocutaneous Syndromes – Sturge-Weber Syndrome
CT demonstrates intracranial dense gyriform calcifications more commonly affect the parieto-occipital cortex.
Gyriform enhancement of the pial angiomatosis
MR is considered to be the standard imaging modality.
T2-weighted sequences demonstrate area of gliosis
Leptomeningeal enhancement, as well as enlargement of the choroid plexus.
GRE images demonstrate calcifications.

39. Neurocutaneous Syndromes – Sturge-Weber Syndrome
Back
Next
Home
Neurocutaneous Syndromes – Sturge-Weber Syndrome a b c
Figure 10: T1 axial post-contrast image demonstrate ipsilateral enhancement and enlargement of the choroid plexus and leptomeningeal enhancement in the right temporal, parietal, and occipital lobes (a & b). Axial non contrast CT demonstrates gyriform calcifications and cerebral atrophy in a different patient (c).

40. Neurocutaneous Syndromes – Tuberous Sclerosis
Back
Next
Home
Neurocutaneous Syndromes – Tuberous Sclerosis
A multisystem disease characterized by hamartomatas in multiple organ systems, including the CNS [5].
Incident of 1/6000 live birth.
Neurological symptoms include seizures, intellectual disability, and behavior problems.
Seizures can present any time, usually as partial seizure secondary to cortical tubers.
80% of patients presents with epilepsy.
MRI may demonstrate multiple cortical tubers, subependymal giant cell astrocytomas, & linear white matter abnormalities.

41. Neurocutaneous Syndromes – Tuberous Sclerosis Complex
Back
Next
Home
Neurocutaneous Syndromes – Tuberous Sclerosis Complex a b c
Figure 11: T1 axial post contrast image demonstrate an enhancing subependymal lesion in the left periventricular region (a). FLAIR axial and coronal images demonstrates cortical tubers (b & c)

42. Conclusion
A significant proportion of medication refractory epilepsy have underlying structural lesions that can be identified with MR imaging.
Familiarity with a few key imaging and clinical features of these diseases can help the radiologist arrive at the correct diagnosis.

43. References Back Next Home
1. Trichard M, Léautaud A, Bednarek N, Mac-Caby G, Cardini-Poirier S, Motte J, Hoeffel C. “Neuroimaging in pediatric epilepsy”. Arch Pediatr May; 19:
2. CP, Panayiotopoulos. The Epilepsies: Seizures, Syndromes and Management. Bladon Medical Publishing. Oxfordshire. 2005,
3. Jung da E, Lee JS. “Multimodal neuroimaging in presurgical evaluation of childhood epilepsy”. Korean J Pediatr August; 53:
4. Rastogi S, Lee C, Salamon N. “Neuroimaging in pediatric epilepsy: a multimodality approach.” Radiographics. 2008 Jul-Aug;28(4):
5. Osborn AG. Osborn’s Brain: Imaging, Pathology, and Anatomy. Lippincott Williams & Wilkins. Salt Lake City, UT   
6. Mathern GW, Babb TL, Vickrey BG, Melendez M, Pretorius JK. “The clinical-pathogenic mechanisms of hippocampal neuron loss and surgical outcomes in temporal lobe epilepsy”. Brain. 1995; 118(pt 1): 105–118.
7. Blumcke I, Lobach M, Wolf HK, Wiestler OD. “Evidence for developmental precursor lesions in epilepsy-associated glioneuronal tumors”. Microsc Res Tech. 1999; 46:53–58.
8. Leventer RJ, Guerrini R, Dobyns WB. “Malformations of cortical development and epilepsy”. Dialogues Clin Neurosci. 2008; 10(1):
9. Leventer RJ et al. “Clinical and imaging heterogeneity of polymicrogyria: a study of 328 patients”. Brain May; 133(Pt 5):
10. Barkovich AJ. “MRI analysis of sulcation morphology in polymicrogyria”. Epilepsia 2010; 51: 17–22.
11. De Ciantis et al. “Ultra-High-Field MR Imaging in Polymicrogyria and Epilepsy”. AJNR 2015; 36: 309 –16

44. THANKS FOR VIEWING OUR PRESENTATION Please send questions or comments to: yuf@uthscsa.edu