Clinical and Surgical Pearls in
Imaging Epilepsy
Neil U. Lall1, Justin M. Honce1, Hisham M. Dahmoush2, Eric M.
Nyberg1, David M. Mirsky3, Lidia M. Nagae1
1Department of
Radiology, University of Colorado, Aurora, CO
Radiology, The Children's Hospital of Philadelphia, Philadelphia, PA
3Department of Radiology, Children's Hospital Colorado, Aurora, CO
2Department of
ASNR 2015 Annual Meeting
eEdE #: eEdE-86a
Control #: 511
Disclosures
• No Disclosures
Educational Objectives/Approach
After viewing this exhibit, the learner will:
A. Understand the role of imaging in the evaluation
and treatment of epilepsy.
B. Be familiar with imaging findings of temporal and
extratemporal epilepsy.
C. Recognize imaging findings related to antiepileptic medications.
D. Understand MRI safety issues associated with
anti-epileptic implantable devices such as vagal
nerve and deep brain stimulators.
Epilepsy
• Definition = Enduring predisposition to generate seizures.
• Affects >4 million people (3% individual lifetime risk).
• Substantially decreases quality of life:
– Threats to physical safety.
– Generation of new epileptogenic foci (may ↑ seizure
frequency/duration).
– Epileptic encephalopathy or Sudden unexpected death in epilepsy
(SUDEP).
• Medical treatment fails in 30% of cases.
• Surgical management ↓ health care costs and ↑ quality of life.
– Success rate is related to the epileptogenic zone.
• Epileptogenic
Click to DefineZone
the Epileptogenic
Zone.
= Area of cortex
indispensable for generation of
seizures. Aimed to be completely resected/disconnected for
control of seizures. May or may not be identifiable on imaging.
Mesial Temporal Sclerosis
• Most common form of focal epilepsy, also with the highest surgical success
rate.
• Coronal oblique images for evaluation of internal architecture of
hippocampus (perpendicular to its main axis).
• Click
to Reveal
Findings.
Epileptic
patient:
Hippocampal asymmetry highlights abnormal T2
hyperintense signal, volume loss, and loss of internal architecture.
Normal (Non-Epileptic) Patient
Epileptic Patient
Mesial Temporal Sclerosis
Left hippocampal
• Primary Findings: Click
to Reveal. volume loss, T2
hyperintensity (gliosis), and architectural distortion.
Volume
loss of ipsilateral
• Secondary Findings: Click
to Reveal.
mammillary body and fornix is common.
Coronal Oblique T2 Images
Mesial Temporal Sclerosis
•
•
Earlier Stages: Enlarged hippocampus with T2 hyperintense signal.
• Ddx: post-ictal changes, low grade glioma, cortical dysplasia, or encephalitis.
MRI negative in 20-30%. MRS, PET, or SPECT may provide lateralization.
– Best postoperative results with abnormalities on MRI.
•
15% “Dual Pathology” = coexistence with other potentially epileptogenic lesions.
– Cortical dysplasia, vascular malformation, tumor, injury, neurocysticercosis,
microencephalocele.
– Controversial cause-effect relationship and surgical approach.
•
Heterotopic
gray
matter
nodule more posteriorly (same patient as prior slide).
Click
to Reveal
Dual
Pathology.
Autoimmune Voltage Gated Potassium
Channel Encephalitis
•
•
•
•
Newly described treatable cause of epilepsy, dementia, and psychiatric symptoms.
Patients respond to immunotherapy rather than anti-epileptic medications.
Unilateral or bilateral enlargement of the amygdala and hippocampus
Possible diffusion restriction/mild enhancement.
•
•
Axial T2 FLAIR: mild enlargement and T2 hyperintensity of the right hippocampus.
Coronal post-contrast T1: mild post-contrast enhancement of the right hippocampus.
Epileptogenic Neoplasms
(Gliomas, gangliogliomas, and DNETs)
• Surgical resection usually 1st choice of treatment
regardless of medical intractability.
• Gliomas (astrocytomas, oligodendrogliomas, and
oligo-astrocytomas).
– Infiltrative, expansile lesions, T2 hyperintense signal.
– Enhancement can be seen in higher grade neoplasms.
• Gangliogliomas (0.4-7.6% of CNS tumors) highly
associated with intractable seizures.
Dysembroplastic Neuro Epithelial
Tumor
•
•
Benign neoplasm (Rare malignant transformation described in literature).
Characteristic imaging findings:
–
–
–
Cortically based, wedge-shaped, rare enhancement, T2 bright lesions with minimal mass effect/edema.
Calvarial remodeling.
“Bubbly appearance” of the lesion with internal septations very suggestive.
T2 STIR
T2 FLAIR FS
T1 Post Contrast
Transmantle tumor with indistinct gray-white matter differentiation of associated cortical dysplasia
Cerebral Cavernous Malformations
• Most common epileptogenic vascular lesions: arteriovenous
malformations and cavernous malformations.
• No intervening brain parenchyma (as opposed to AVMs).
• 4% of the population.
• Imaging findings:
–
–
–
–
Central heterogeneous blood products of various ages and calcification.
Minimal edema/mass effect.
Usually absent or faint post-contrast enhancement.
Classic circumferential hemosiderin (hypointensity on T2, prominent
susceptibility on T2*).
• Associated developmental venous anomaly in up to 26%.
– Surgical preservation to avoid venous infarct.
• Complete resection should include epileptogenic hemosiderin rim.
– 20-30% have multiple lesions (typically familial): epileptogenic source should
be identified to guide surgery.
Cerebral Cavernous Malformations
• Axial T2* GRE image: Multiple foci of gradient susceptibility
corresponding to cavernous malformations.
• Axial
Click to
Reveal
Additional
Images. restriction from status
DWI
image:
Cortical diffusion
epilepticus.
Malformations of Cortical
Development
• Neuroblasts and glioblasts travel along radially oriented glial fibers,
“inside-out” from periventricular region  cortical plate.
• In utero neuronal migrational abnormalities may occur during:
– Neuronal–glial proliferation and differentiation.
– Neuronal migration to the cortical plate.
– Final stages of intracortical organization.
• Disorders include:
–
–
–
–
–
Focal cortical dysplasia.
Agyria/pachygyria/band heterotopia spectrum.
Polymicrogyria.
Schizencephaly.
Nodular heterotopias.
• Subependymal (more common) or subcortical variant.
Focal Cortical Dysplasia
•
•
3rd most common epileptogenic lesion in children (after hippocampal sclerosis and tumors).
Findings subtle; Most pronounced in Type IIb (balloon cell) with abnormal white matter signal.
–
–
•
•
MRI normal in up to 34%.
Other findings: mild focal volume loss, gyral simplification, or blurring of gray-white margins.
Treatment: Resection of dysplastic area (MRI often does not reveal entire extent).
Hyperintense
in transmantle pattern from ependyma to cortex (reflecting radially oriented
Click
to Revealsignal
Findings.
glial fibers) + indistinct gray-white matter differentiation.
Axial T2 FLAIR
Agyria/Pachygyria/Band Heterotopia
•
Spectrum of the related genetic causes (primarily DCx and LIS1).
–
•
•
•
Agyria (lissencephaly) = Most severe. Smooth hourglass configuration to brain, no sylvian fissures.
Pachygyria = simplified gyral pattern (broad gyri with shallow sulci).
Band heterotopia = heterotopic band of gray matter between the germinal matrix and the cortex.
–
•
Incomplete migration of superficial layers of cortex.
Milder female heterozygous form.
Click
to Reveal
“Double
cortexFindings.
sign” = Thin band of white matter separating cortex from heterotopic gray matter.
Axial T1
Polymicrogyria
• Late migrational failure with abnormal development of
deep layers of the cerebral cortex.
• Possible Etiologies: In utero infections (CMV) and vascular
insults.
• Associations: Chiari malformation, schizencephaly,
numerous syndromes.
• Imaging findings:
– Innumerable small disorganized gyri, with irregular cortical
thickening.
– Can be confused with thickened cortex of pachygyria.
• Irregular gray-white junction and crowded cortical pattern
differentiate polymicrogyria.
• Resection may cure epileptogenic unilateral polymicrogyria.
Schizencephaly with Polymicrogyria
•
•
•
•
Polymicrogyria may line schizencephalic cleft or present in a “mirror-image” contralateral location.
Closed-lipped
Click
to Revealschizencephalic
Findings.
defect (tightly apposed gray matter cleft).
Clues:toDimple
Click
Revealalong
Findings.
surface of right lateral ventricle, focal enlargement of CSF (at times shows
prominent vessel).
Click
to Reveal
Findings.
Sagittal
demonstrates
associated polymicrogyria.
Axial T2 FLAIR
Coronal T1
Sagittal T1
Nodular Subependymal Heterotopia
•
•
•
•
•
•
Single or multiple nodules along ependymal surface of the ventricles (unilateral or bilateral).
When diffuse and symmetric, consider underlying genetic cause.
Commonresection
Surgical
associations:
of nodules
callosaland
hypo-/agenesis
corresponding
and
dysplastic
ipsilateral
cortex
basalfor
ganglia
medically
dysmorphia.
refractory epilepsy.
– Seizure-free
outcome
of surgery
more favorable indysplastic
unilateral cases
than
Surgical
resection
of nodules
and corresponding
cortex
forbilateral.
medically refractory epilepsy
Images:
Nodularoutcome
heterotopic
gray more
matter
lines the
bilateralcases
lateral
ventricles.
– Seizure-free
of surgery
favorable
in unilateral
than
bilateral
Images:
Common
Nodular
associations:
heterotopic
Callosal
gray
dysgenesis
matter lines
and the
cerebellar
bilateralmalformation
lateral ventricles.
shown below.
Click
to Reveal
Findings.
–
Click to reveal
Additional
associations
other findings:
include ipsilateral basal ganglia dysmorphia.
Axial T1
Axial T2
Sagittal T1
Nodular Subcortical Heterotopia
•
•
•
Swirling, curvilinear or nodular mass of gray & white matter which may extend
from cortex to ventricle.
Anomalies such as callosal hypo-/agenesis and ipsilateral basal ganglia dysmorphia
commonly associated.
Abnormalities/epileptogenic activity extends beyond imaged nodules:
– Resection of corresponding dysplastic cortex also required.
Coronal T2 STIR
Axial T1 non-contrast
Neurocutaneous Syndromes
•
•
Congenital abnormalities with common facial stigmata, intellectual disabilities, and
seizures.
Tuberous Sclerosis
– Classic clinical triad of epilepsy, facial angiofibroma (adenoma sebaceum), and mental
retardation.
– Cortical/subcortical tubers, subependymal nodules, and subependymal giant cell
astrocytomas (SEGAs).
– Dominant tuber resection can reduce seizure frequency, often improving neuropsychological
development.
•
α-[11C] methyl-L-tryptophan (AMT) PET may identify which of multiple tubers are epileptogenic
– Some recently effectively treated with mTOR1 inhibitors such as Everolimus
•
Sturge-Weber Syndrome
– Congenital facial nevus, epilepsy, and ocular abnormalities.
– Asymmetric developmental myelination pattern, presumably due to early subclinical seizures.
•
Affected hemisphere with accelerated myelination  low signal on T2WI and high signal on T1WI.
– Refractory epilepsy may benefit from hemispherectomy to control seizures and allow
neurodevelopment.
Tuberous Sclerosis
•
Conspicuous white matter radial migration lines (T2)
–
•
•
•
Represent heterotopic neuronal/glial migrational arrest, Tuber often located at associated cortical surface.
Tubers poorly identifiable on T2 within background of hyperintense unmyelinated white matter.
Tubers and subependymal nodules hyperintense on T1; lesions near foramen of Monro concerning
for SEGA.
Interval
myelination
numerous cortical tubers conspicuous. Additionally note prominent
Click
to Reveal
Followmakes
Up Images.
perivascular spaces.
T2
T1 MPRAGE
2 days of age
T2
32 months of age
Sturge-Weber Syndrome
•
•
CT: Characteristic “tram-track” cortical calcifications
MRI (different patient): Hemispheric atrophy and gyriform T1 shortening (from calcification);
extensive leptomeningeal enhancement of angioma and enlarged ipsilateral choroid plexus.
–
Contralateral small leptomeningeal angioma may ↓ success rate of surgery.
Noncontrast CT
T1
T1 FS Postcontrast
Rasmussen’s Encephalitis
• Rare but severe progressive unilateral hemispheric
atrophy
– Associated neuropsychological dysfunction, and intractable
seizures.
• Though immune-mediated, response to
immunotherapy or AED is poor.
• Effective treatment: (functional) hemispherectomy or
hemispherotomy.
– Up to 80% long-term seizure-free outcomes.
Neuropsychological decline may be halted.
– Significant deficits: Homonymous hemianopsia and
hemiplegia (if not present pre-operatively). May regain
ability to walk independently.
Rasmussen’s Encephalitis
•
Early signs before hemispheric volume loss is conspicuous:
– Ipsilateral ventricular enlargement and volume loss in the basal ganglia and perisylvian region.
– FDG-PET and SPECT may show diffuse unilateral hypometabolism or altered perfusion.
•
•
Cortical/subcortical T2 hyperintensity and overlying cortical thinning.
Increased
Click
to Reveal
T2 signal
Findings.
in left insula. Regional volume loss with enlarged Sylvian
fissure.
Axial T2 FLAIR
Coronal T1
Hypothalamic Hamartoma
•
•
•
•
•
Benign congenital malformation of heterotopic mature neurons and glial cells in
tuber cinereum
Sessile (rather than pedunculated) form commonly with seizures (typically gelastic)
Non-enhancing. Calcifications are very rare
Seizures typically refractory to medications.
Surgical options: Resection or disconnection of the hamartoma, stereotactic
thermocoagulation, and gamma knife surgery.
Suprasellar mass
isointense to
gray matter.
Click to Reveal
Findings.
Sagittal T1 MPRAGE
Non-Lesional Epilepsy Evaluation
• SPECT
– Evaluates regional cerebral blood flow in epileptic patients
– Both during the ictal period and the interictal period.
• Epileptogenic focus: Ictal hyperperfusion and interictal hypoperfusion.
• “Subtraction” images often beneficial.
– Agents: Tc-99m hexamethyl-propylene amine oxime (HMPAO)
and Tc-99m ethyl cysteinate dimer (ECD).
• Trapped after 1st pass (in seconds) = Able to assess ictal blood flow.
• F-18 fluorodeoxyglucose (FDG) PET
– Indirectly measures neuronal function via glucose metabolism.
• Epileptogenic focus is hypometabolic in interictal period.
– Requires 30-60 minutes for radiotracer uptake and distribution.
• Largely restricts utility to interictal evaluation.
Ictal and Interictal SPECT
• Axial ictal SPECT images fused with MRI in a patient with non-lesional
epilepsy.
• Click
to Reveal
Findings.
Left frontal
cortex:
↑ ictal and concordant mildly ↓ interictal blood flow.
Ictal
Interictal
Interictal PET
• Axial PET image fused with MRI in a patient with non-lesional epilepsy.
Hypometabolism
in right perirolandic cortex suggests epileptogenic focus.
• Click
to Reveal Findings.
Implantable Devices and MRI Safety
• Alternatives to resection: Vagal nerve stimulator or deep brain
stimulator.
– Require transmit/receive head coil: Transmit RF body coils are
contraindicated.
• Risk of heating injury and/or damage system components in the neck.
• Neck, cervical, and thoracic MRI cannot be performed.
• However possible to image extremities and lumbar spine with local transmit
RF coils.
• Patients worked up for surgery may have intracranial monitoring
strips/grids/electrodes.
– Generally only may image using transmit RF body coil in combination
with receive-only surface coil.
– Thus incompatible with vagal nerve stimulator or deep brain
stimulator.
• Low SAR protocols: Refer to manufacturer guidelines to determine
field strength compatibility with 3.0T.
Imaging Findings on Anti-Epileptic Drugs
• Phenytoin: Cerebellar volume loss and calvarial
thickening.
• Valproate: Encephalopathy and reversible
cerebellar volume loss.
• Vigabatrin
– Irreversible inhibitor of GABA transaminase.
– 1st line therapy for infantile spasms.
– May cause T2 prolongation and diffusion restriction.
• More common in younger infants or on high dose therapy.
• Possibly due to intramyelin edema.
Vigabatrin Toxicity
•
Abnormal signal possible in thalami, globus palladi, anterior commissure, dorsal
brainstem, corpus callosum, or dentate nuclei.
– Most asymptomatic, but extrapyramidal symptoms and acute encephalopathy may develop.
•
•
Click
to Reveal
Findings.
Restricted
diffusion
of thalami and globus palladi.
Discontinuation/reduction
usually results in resolution.
Click
to Reveal Follow Up Imaging.
DWI Images - Initial Scan
8 Month Follow Up
Treatment-Related MRS Changes
• Propan-1,2-diol (1,2-PD)
– Vehicle for IV anti-epileptic
drugs.
– Doublet peak at 1.14 ppm.
– Not to be confused with lactate
peak (1.33 ppm).
• Acetone
– Anti-epileptic ketogenic diet.
– Singlet peak at 2.22 ppm.
– Intraventricular CSF spaces and
brain parenchyma.
1,2-PD
Acetone
PPM 4.0
3.0
2.0
1.0
Lac
PPM 4.0
3.0
2.0
1.0
PPM 4.0
3.0
2.0
1.0
Discussion/Summary
• There are a wide variety of causes of lesional epilepsy, including
mesial temporal sclerosis, neoplasias, cavernous malformations,
channelopathies, neurocutaneous syndromes, and malformations
of cortical development.
• The radiologist’s participation in the clinical and surgical
management of patients with epilepsy is key, and familiarity with
concepts and approaches is mandatory.
• Imaging findings in lesional and non-lesional refractory seizure may
impact management.
• Vagal nerve stimulators and deep brain stimulators require similar
MRI precautions which are generally incompatible with restrictions
of intracranial monitoring strips/grids/electrodes.
• Anti-epileptic medications may result in varying imaging effects,
some on MRI and some on MRS.
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•
•
•
•
•
•
•
•
•
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