CURRENT TRENDS

IN IMAGING OF

EPILEPSY

PRESENTED BY

Dr Sameer Peer MBBS ( Govt. Medical College, Srinagar)

2nd Year MD Radiodiagnosis student

CONSULTANT I/C

PROF. IRFAN ROBBANIPROFESSOR

DEPARTMENT OF RADIODIAGNOSIS & IMAGING

SR I/C

DR ZUBAIR AHMADSENIOR RESIDENTDEPARTMENT OF

RADIODIAGNOSIS & IMAGING

CONTENTS

1. Definitions

2. Who needs imaging?

3. Imaging Protocols

4. Etiology

5. Recent Advances in neuroimaging of epilepsy with review of literature

DEFINITIONS

SEIZURELatin – 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.

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

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 therapy6. Children with myoclonic seizures and infantile spasms presenting in first year

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 ++

MRI Protocols in EpilepsyT1WISuperior 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.FLAIRLook 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 SWIHelpful 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.

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.

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

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 here5. 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.

6. Hemimegalencephaly • Enlarged hemisphere with ipsilateral venticular enlargement

• Only such condition• Hamartomatous growth of one

cerebral hemisphere over itself

• Click here7. 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

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

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

MTS ( Right side) MTS (Left side)

Status epilepticus

DNET mimicking as MTS Click here

Focal cortical dysplasia

FCD – Transmantle signClick here

Ulegyria – mushroom appearance Click here

Cavernoma CLICK HERE

Ganglioglioma – cyst with a mural nodule/calcifications Click Here

DNET – Swollen gyrus, bubbly appearance, little or no enhancement, associated FCD, wedge shaped

Click Here

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

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

Click here

Hemimegalencephaly Click here

Rasmussen’s encephalitis Click here

Tuberous sclerosis – imaging findings Click here

Sturge-weber syndrome – imaging spectrum click here

Polymicrogyria - difference between normal sulcation and polymicrogyria

Click here

HeterotopiaClick here

Schizencephaly Click here

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.)

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)

QUANTITATIVE MRI

• MR Volumetry • Tissue Segmentation techniques • Voxel based morphometry• Texture analysis

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.

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

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

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.

TEXTURE ANALYSIS

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

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

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

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

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

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.

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.

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

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

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

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

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

• 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

THANK YOU