This document provides definitions and classifications of seizures and epilepsy. It discusses who needs neuroimaging for epilepsy and recommends MRI as the best imaging modality. It reviews common MRI protocols and discusses key imaging findings and features of various epilepsy etiologies. Recent advances in neuroimaging for epilepsy are also summarized, including quantitative MRI techniques like volumetry, voxel-based morphometry, and texture analysis as well as advanced techniques like diffusion tensor imaging, tractography, magnetic resonance spectroscopy, and functional MRI.

3. CONTENTS
1. Definitions
2. Who needs imaging?
3. Imaging Protocols
4. Etiology
5. Recent Advances in neuroimaging of epilepsy with review of
literature

4. DEFINITIONS
SEIZURE
Latin – sacire (“to
take possession
of”)
• Paroxysmal event
due to abnormal,
excessive,
hypersynchronous
discharges from a
group of CNS
neurons.
Epilepsy
• Recurrent
Seizures
• Chronic,
underlying
process
• Epilepsy refers
to a clinical
phenomenon
rather than a
single disease
entity
• There are many
causes and forms
of epilepsy
Epilepsy
syndrome
• Clinical and
pathologic
characteristics
are distinctive
and suggest a
specific
underlying
etiology.

5. Classification of seizures
• Focus on particular etiology
• Appropriate therapy
• Prognostication
1981, International League against Epilepsy (ILAE) classification :
SEIZURE
Partial Seizures
• Simple
• Complex
• Secondary
generalized
Primary Generalized
• Absence
• Tonic-clonic
• Tonic
• Atonic
• Myoclonic
Unclassified
• Neonatal
• Infantile
spasms

7. WHO NEEDS IMAGING?
“Not every patient with epilepsy needs imaging”
NEED IMAGING DO NOT NEED IMAGING
1. Focal neurological deficits or
asymmetry
1. Primary (idiopathic) generalized
epilepsy ( Typical absence, Juvinile
myoclonic epilepsy, Grand mal)
2. Neuro-cutaneous syndromes 2. Benign partial epilepsy (
centrotemporal or occipital spikes)
3. Developmental regression 3. Simple febrile convulsions
4. Simple Partial seizures 4. A persistent focal discharge ( spike,
slow,sharp) on a single EEG STUDY
5. Refractory complex partial Seizures (
at least 1 seizure per month, not
responding to anticonvulsant therapy
6. Children with myoclonic seizures and
infantile spasms presenting in first year

8. WHICH IMAGING MODALITY?
MODALITY APPROPRIATENESS
1. MRI with contrast +++
2. MRI without contrast +
3. CT with contrast +
4. CT without contrast +
5. fMRI ++
6. Nuclear Imaging ++

9. MRI Protocols in Epilepsy
T1WI
Superior for cortical thickness and the
interface between grey and white matter.
On T1WI look for grey matter occuring in
an aberrant location as in gray matter
heterotopia.
FLAIR
Look very carefully for cortical and
subcortical hyperintensities on the FLAIR,
which can be very subtle.
Since FLAIR may show false-positive
results due to artefacts, the abnormalities
should be confirmed on T2WI.
T2* or SWI
Helpful when searching for haemoglobin
breakdown products as in posttraumatic
changes and cavernomas, or to look for
calcifications in tuberous sclerosis, Sturge-
Weber, cavernomas and gangliogliomas.

10. Discussion on Etiologies – What to look for?
“EYES CAN’T SEE WHAT THE MIND DOES NOT KNOW”
• Mesial Temporal Sclerosis
• Focal Cortical Dysplasias
• Cortical and Glial Scars – Ulegyria
• Cavernomas
• Epileptogenic tumors – Ganglioglioma, DNET, Pleomorphic
Xanthoastrocytoma, Hypothalamic hamartomas
• Neuro-cutaneous syndromes – Tuberous sclerosis, sturge-weber
• Others – polymicrogyria, schizencephaly, hemimegalencephaly, heterotopia,
Rasmussen’s encephalitis, congenital infections, Dyke-Davidoff-Masson etc.

12. Salient Imaging features of various etiologies
Pathological condition Imaging features
1. Mesial Temporal Sclerosis • Hippocampal Volume loss
• Hippocampal Hyperintensities on
T2/FLAIR ( better on coronal) click
here
2. Focal Cortical Dysplasias • Subtle cortical/subcortical
hyperintensities
• Blurred Grey-white interface
• Often located at bottom of a deep
sulcus
• Transmantle sign click here
3. Cortical / glial scars - ulegyria • Meningitis or perinatal insult
• Ulegyria – specific type of scar
• Cerebral cortical scarring due to
perinatal ischemia
• Ulegyria – pedunculated gyri –
mushroom appearance click here

13. 4. Cavernoma • Cavernous angioma/ cavernous
malformation
• Low flow malformation with a
tendency to bleed
• “Popcorn ball with hemosiderin
rim”
• T2* and SWI most sensitive
• May be associated with DVA
Click here
5. Epilepsy associated tumors
• Ganglioglioma
• DNET
• Pleomorphic Xanthoastrocytoma
• Hypothalamic Hamartoma
These tumours share the following
characteristics:
•They arise in a cortical location.
•Often located in the temporal lobe.
•Closely related to developmental
malformations.
•Typically seen in adolescents and young
adults.
•Characterized by a benign behaviour, a slow
growth, a sharp delineation and usually show
absence of edema.
•Show signs of chronicity, such as bone
remodeling and scalloping of the adjacent
skull.

14. 6. Hemimegalencephaly • Enlarged hemisphere with
ipsilateral venticular
enlargement
• Only such condition
• Hamartomatous growth of one
cerebral hemisphere over itself
• Click here
7. Rasmussen’s encephalitis • Progressive hemiatrophy of the
cerebral hemisphere due to unknown
etiology
• Intractable seizures
• Ipsilateral ventricular enlargement
• Click here
8. Tuberous Sclerosis • hamartomas in many organs
including angiomyolipoma of the
kidney, cardiac rhabdomyoma and
cortical and subependymal tubers in
the brain.
• Cortical hamartomas, subependymal
tubers, SEGA, white matter
abnormalities. Click here

15. 9. Sturge – Weber syndrome • Sturge-Weber is also called
encephalotrigeminal
angiomatosis.
• It is a vascular malformation
with capillary venous
angiomas in the face (port-
wine stain), choroid of the
eye and leptomeninges.
• Leptomeningeal
enhancement
• Cortical tram-track
calcifications
• Atrophy mainly posteriorly
• Click here
10. Polymicrogyria • Numerous small gyri
• Predilection for Sylvian fissure
• Atrophy mainly posteriorly
• Anomalous venous drainage in
areas of polymicrogyria
• Click here

16. 11. Heterotopia Heterotopic Grey Matter results
from an arrested migration of
normal neurons along the radial
path between the ventricular walls
(ependyma) and the subcortical
regions.
There are two types of heterotopia:
subependymal and subcortical.
The most common clinical
presentation is intractable seizures.
Heterotopia present as nodular foci
of grey matter intensity on all
sequences. They do not enhance.
Click here
12. Schizencephaly Schizencephaly is a cleft in the brain that
connects the lateral ventricle to the
subarachnoid space.
The cleft is lined by polymicrogyric gray
matter.
Open-lip schizencephaly is characterized
by separation of the cleft walls.
Closed-lip schizencephaly is
characterized by cleft walls in apposition
to each other. Click here

18. MTS ( Right side) MTS (Left side)

19. Status epilepticus
DNET mimicking as MTS
Click here

20. Focal cortical dysplasia

21. FCD – Transmantle sign
Click here

22. Ulegyria – mushroom appearance Click here

23. Cavernoma CLICK HERE

24. Ganglioglioma – cyst with a mural
nodule/calcifications Click Here

25. DNET – Swollen gyrus, bubbly appearance, little or no
enhancement, associated FCD, wedge shaped
Click Here

26. PXA – Supratentorial cyst with mural
enhancement, abutting meninges, meningeal
enhancement Click Here

27. Hypothalamic hamartoma – non-enhancing
enlargement of the tubercinerium of the
hypothalamus- - precocious puberty, gestaltic seizures
Click here

28. Hemimegalencephaly Click here

29. Rasmussen’s encephalitis Click here

30. Tuberous sclerosis – imaging findings Click here

31. Sturge-weber syndrome – imaging spectrum click here

32. Polymicrogyria - difference between
normal sulcation and polymicrogyria Click here

33. Heterotopia
Click here

34. Schizencephaly Click here

35. Recent Advances in imaging of Epilepsy with review
of literature
1. Reformatted Images –
- 3D volume data
- T1 weighted inversion recovery (IR, SPGR, MPRAGE etc.)
- Thin sections ( < 1.5 mm)
- MPR/CPR
Achten E. et al proposed a MR protocol for presurgical evaluation of
patients with complex partial seizures in which T1 weighted paracoronal
inversion recovery sequences and volume measurements were considered
as essential, while T2 weighted images could be avoided
(Achten E, Boon P, De Poorter J et al. An MR protocol for presurgical
evaluation of patients with complex partial seizures of temporal lobe
origin. AJNR Am J Neuroradiol. 1995 Jun-Jul;16(6):1201-13.)

36. MPR and CR analysis add to the neuroimaging evaluation of FCD by improving the
lesion diagnosis and localization. CR helps to establish the extent of the lesion more
precisely, allowing the visualization of some areas not shown on high resolution MRI
and MPR. These techniques are complementary and do not replace the conventional
wisdom of MRI analysis.
(Montenegro MA, Li LM, Guerrerio CA, Cendes F. Focal cortical dysplasia: improving
diagnosis and localization with magnetic resonance imaging multiplanar and
curvilinear reconstruction. J Neuroimaging. 2002 Jul;12(3):224-30)

38. QUANTITATIVE MRI
• MR Volumetry
• Tissue Segmentation techniques
• Voxel based morphometry
• Texture analysis

39. Farid et al. Temporal Lobe Epilepsy : Quantitative MR Volumetry in Detection of
Hippocampal Atrophy. Radiology: Volume 264: Number 2—August 2012
• Purpose: To determine the ability of fully automated volumetric magnetic
resonance (MR) imaging to depict hippocampal atrophy (HA) and to help
correctly lateralize the seizure focus in patients with temporal lobe epilepsy
(TLE).
• Material and methods : Volumetric MR imaging data were analyzed for 34
patients with TLE and 116 control subjects. Structural volumes were calculated
by using U.S. Food and Drug Administration–cleared software for automated
quantitative MR imaging analysis (NeuroQuant). Results of quantitative MR
imaging were compared with visual detection of atrophy, and, when available,
with histologic specimens. Receiver operating characteristic analyses were
performed to determine the optimal sensitivity and specificity of quantitative
MR imaging for detecting HA and asymmetry.
• Quantitative MR imaging can depict the presence and laterality of hippocampal
atrophy in TLE, with accuracy rates for seizure lateralization of 88% versus the
76% achieved with visual inspection of clinical MR imaging studies.

40. Statitical probabilistic hippocampal sub-fields
Multi-contrast submillimetric 3 Tesla hippocampal subfield
segmentation protocol and dataset
Jessie Kulaga-Yoskovitz, Boris C. Bernhardt, Seok-Jun Hong, Tommaso
Mansi, Kevin E. Liang, Andre J.W. van der Kouwe, Jonathan Smallwood,
Andrea Bernasconi & Neda Bernasconi, Scientific data, 10th Nov 2015

42. VOXEL BASED MORPHOMETRY
• Voxel-wise comparison of the “local concentration” of some property ( e.g. signal )
between two groups
• There must be accurate co-registration of images before comparison
• Linear registration – to conform all brains to same orientation and size
• Non-linear registration – to conform all subjects to a common reference volume

43. MTLE shows T1 signal reduction due to hippocampal sclerosis – VBM can be
useful in mapping areas of abnormal signals.
VBM has been used to indicate region specific abnormalities in TLE, hippocampal
atrophy, MCDs, JME etc.

44. TEXTURE ANALYSIS
• 3D T1W images
• Voxel wise operators are used to assess FCDs
• Cortical thickness, gray-white interface quantification.

45. MRS in epilepsy
• Non-invasive method
• Lateralization, detecting bilateral abnormalities, Identifying epileptogenic foci
• Proton spectroscopy is most frequently utilized.
• Metabolites – NAA, Cho, Cr, Lac, Glx (Glutamine/glutamate), mI.
• Both Absolute and relative values are obtained.
• DECREASED NAA indicates neuronal loss, INCREASED Cho and Cr levels indicate
gliosis/astrocytosis
• NAA/Cho+Cr ratio – simplest and single most useful index
• Lac levels increase soon after seizure
• Increased mI levels – gliosis and irreversible parenchymal damage
• Glx levels indicate glutamate levels in neurons – potential epileptogenic focus even if
routine MRI is normal.
• Reduced NAA levels are also note in contralateral side – indicates neuronal/glial
dysfunction rather than neuronal loss – reversible after surgery
• Extra-temporal epilepsy, ability to lateralize is less – 50% in frontal lobe epilepsy

46. T2 RELAXOMETRY
T2 relaxometry of the hippocampi as a means of identifying MTS was originally
described by Jackson et al, who used a 16- echo-train Carr-Purcell-Meiboom-
Gill (CPMG) sequence fitted to a monoexponential T2 decay curve.
Duncan et al (AJNR 17:1811–1814, Nov 1996) replaced the Jackson-Connelly
16-echo CPMG sequence with a double spin-echo pulse sequence that provides
wholehead anatomic coverage and serves the dual purposes of routine diagnostic
MR evaluation and estimation of hippocampal T2 relaxation.
Example of a T2 map from a 2-year-old child
showing a region of interest within the left
hippocampus

47. Diffusion Tensor Imaging and Tractography
• DTI studies the motion of water molecules at voxel level
• Provides quantitative and reproducible data e.g. mean diffusivity and fractional
anisotropy, to assess structural integrity of brain.
• Diffusion studies can be done in ictal/peri/post ictal and interictal periods
• Tractography is post acquisition processing extension of DTI in which
directional information of diffusion of water in each voxel is used to infer
orientation of specific white matter tracts.
• Once specific pathways are isolated, anatomy can be visualized quantitatively
and qualitatively.
• This information is useful in pre-operative planning, to delineate relationships
of eloquent cortex with planned operative site, visualization of language and
memory pathways, assessment of visual pathway ( meyer’s loop) preoperatively
to reduce risk of contralateral superior homonymous field defects

49. Magnetic resonance imaging/diffusion tensor imaging tractography used to
compare white-matter tracts in a control individual with those in a patient with
mesial temporal-lobe epilepsy. Note the diminished connectivity between the
posterior cingulate cortex, the precuneus, the medial prefrontal cortex, and the
medial temporal lobes. (Liao et al, Altered functional connectivity in
default mode network in absence epilepsy: a resting state fMRI study.
Hum Brain Mapp. 2011;32:438–449

50. FUNCTIONAL MRI (fMRI)
• Pre – operative localization of motor strip
• Language localization
• Identifying memory laterality
FMRI paradigms that produce bilateral MTL activation of MTL structures in the
healthy control subjects are ideal for the presurgical evaluation of memory function
in the TLE patients. Novelty scene encoding paradigm is suitable for this
purpose that has shown an asymmetry of activation between the affected and
unaffected MTL structures in patients with TLE .
Greater hippocampal activation contralateral to the epileptic focus may indicate low
risk of developing global amnesia. However, it is less reliable in predicting the
postoperative memory deficits because the activation in that hemisphere may partly
reflect brain reorganization with shift of activation from the epileptic hemisphere.
The shifted activation may not necessarily represent functionally meaningful
memory. In other words, a large area of activation on the contralateral side may
serve as a compensatory mechanism and the patients may still have postoperative
memory decline.

51. Richardson et al. noted that activation of the right hippocampus during a verbal
memory task in the left TLE patients was “dysfunctional” and it did not predict
memory function postoperatively .
This was recently confirmed in a study by Binder et al. in which they compared
the predictive value of language lateralization and scene encoding task paradigms.
They found that hippocampal activation asymmetry during scene encoding was
strongly correlated to the side of seizure focus and memory asymmetry scores in
Wada test but it was unrelated to verbal memory outcome.

52. Role of Functional MRI in Presurgical Evaluation of Memory Function in
Temporal Lobe Epilepsy, Chusak Limotai and Seyed M. Mirsattari,
Epilepsy Research and Treatment, Volume 2012 (2012), Article ID 687219,
12 pages

53. MAGNETO-ENCEPHALOGRAPHY
• Non-invasive tool for localization of epileptic focus
• Measures extra-carnial magnetic fields perpendicular to direction of intra-
cellular currents in apical dendrites
• Magnetic fields are minimally affected by intervening structure between brain
and scalp ( advantage over EEG)
• Useful in pediatric population for identifying epileptogenic focus as neocortical
epilepsy is more common than MTLE.
• Disadvantage – poor localization of deeper foci e.g. MTLE
• MEG is better than fMRI in pre-surgical mapping of eloquent cortex
• MEG also has greater value in post-surgical epileptic focus determination as
magnetic field is relatively insensitive to brain defects and brain volume changes

55. Positron Emission Tomography in Epilepsy
• PET has been the first functional neuroimaging technique applied to presurgical
evaluation of pharmacoresistant focal epilepsies, in the late seventies, before MRI was
available.
• It used the [18F]-Fluorodeoxyglucose (FDG) to obtain images of interictal brain
glucose metabolism.
• It was particularly useful in patients with a normal brain CT scan, showing a focal
interictal glucose hypometabolism.
• FDG PET remains today a routinely used examination in the presurgical assessment
of drug refractory focal epilepsies.
• Focal interictal hypometabolism on FDG PET is usually associated with seizure foci,
but hypometabolism is typically larger than the epileptogenic cortex, reflecting the
altered neuronal function in the ictal focus and possibly extending to the areas of first
ictal spread

56. In current clinical practice, FDG PET is usually acquired on PET/CT scanners,
although recent developments suggest that the newly available PET/MRI hybrid
modality might play a relevant role
Valentina Garibotto and Fabienne Picard, Nuclear Medicine Imaging in Epilepsy,
Epileptologie 2013; 30: 109 – 121

57. SPECT in epilepsy
• The clinical observation that during a seizure there is an increase in cortical
blood flow was initially directly observed during brain surgery by Sir Victor
Horsley, more than a century ago.
• SPECT studies involve CBF imaging using radiopharmaceuticles, Tc99-
Hexamethypropyleneamine oxime or Tc99-bisicate which have a rapid first
pass brain extraction.
• Maximum uptake occurs 30-60 minutes after IV injection. Acquisition can be
done 4-5 hrs later, so that patient can recover before imaging
• Ictal and interictal scans are obtained.
• Interictal scans serve as baseline. On ictal scans, areas of hyperperfusion are
identified.
• Interictal scans by themselves have low sensitivity for MTLE. Ictal scans have
poor spatial resolution as compared with PET.
• Normalized and coregistered interictal scans are subtracted from ictal images

58. • Subtracted images are superimposed on a high resolution MR using software
package such as Subtraction ictal SPECT coregistered to MR imaging ( SISCOM)
Valentina Garibotto and Fabienne Picard, Nuclear Medicine Imaging in
Epilepsy, Epileptologie 2013; 30: 109 – 121