Recommendations for Neuroimaging of Patients with Epilepsy

Techniques

Scans must be interpreted in the context of the entire clinical situation. A specialist in neuroimaging, who has training and expertise in the neuroimaging of epilepsy, must review the images.

Magnetic resonance imaging is the structural imaging tool of choice.^2,3 It is superior to radiographic CT in terms of both sensitivity and specificity for the identification of small lesions and abnormalities of the cerebral cortex. Even when a CT scan reveals an epileptogenic lesion, MRI often adds new and important data in terms of characterising the nature and extent of the underlying pathology and identifying other lesions.

The principle role of MRI is in the definition of the structural abnormalities that underlie seizure disorders. Hippocampal sclerosis may be reliably identified (Figure 3.1), while quantitative studies are useful for research and, in equivocal cases, for clinical purposes. A range of malformations of cortical development may be determined (Figures 3.2 –3.4). The proportion of cryptogenic cases of epilepsy has decreased with improvements in MRI hardware, signal acquisition techniques and post-processing methodologies (Figure 3.5).

Figure 3.1

Coronal and Axial T1-Weighted MRI Scan Showing Right Hippocampal Sclerosis (Arrow). Figure courtesy of Dr Rod C. Scott, Institute of Child Health, London.

Figure 3.2

Examples of Malformations of Cortical Development Documented with MRI. Top: Axial T1-weighted MRI scan showing bilateral schizencephaly (arrows). Bottom left: Coronal T1-weighted MRI scan showing right focal cortical dysplasia (arrows).

Figure 3.3

Posterior Agyria–pachygyria with Polymicrogyria Documented with MRI Scan in Two Brothers. Axial T2-weighted MRI scans from the older (top) and younger (bottom) brothers. There is marked posterior agyria–pachygyria (more...)

Figure 3.4

Small Malformations of Cortical Development Documented with MRI. Left: coronal T2-weighted MRI scan showing frontal focal cortical dysplasia (arrow). Figure courtesy of Dr Rod C. Scott, Institute of Child Health, London.

Figure 3.5

Magnetisation Transfer Ratio Maps. Axial images. Magnetisation transfer ratio maps for 30 control subjects (A and D) and patients with normal conventional MRI and left temporal lobe epilepsy (B) and right temporal lobe epilepsy (more...)

Both T1-weighted and T2-weighted images should be obtained, with slices as thin as possible. Three-dimensional volume acquisition is preferable, but coronal as well as axial slices should be obtained in all cases. Gadolinium contrast enhancement is not necessary in routine cases, but may be helpful in selected cases if the non-contrast-enhanced MRI scan is not definitive. Myelination is incomplete in the first 2 years of life, thereby resulting in a poor contrast between white and grey matter and, thus, producing difficulties in detecting cortical abnormalities. In contrast, white matter disorders are recognised better, since the normal signal of myelin (which varies according to age) and the topography of the brain are well known. In such young patients, MRI scans may not reveal lesions and scans may have to be repeated again after 1–2 years.²

However, it should be emphasised that certain lesions such as focal cortical dysplasia are not always identified with conventional MRI and may be more easily identified on a fluid-attenuated inversion recovery (FLAIR) sequence by reconstructing the imaging data set in curvilinear planes and by quantitative assessment of the signal and texture.^15,25

A fluid-attenuated inversion recovery sequence increases the conspicuity of lesions (Figure 3.6) that may not otherwise be identified and this sequence should be part of a standard MRI protocol for patients with epilepsy. Other sequences, such as T2, may reveal abnormalities such as small cavernous angiomas.

Figure 3.6

Series of Coronal MRI Scans Showing Increased Lesion Conspicuity with Flair. The patient’s left is on the right of the images. The patient is a 50-year-old man with a 25-year history of focal motor seizures involving the right (more...)

In addition to careful qualitative evaluation of the hippocampus, quantitative assessment can be useful. Hippocampal volumetry requires absolute volumes corrected for the intracranial volume, which must be compared with appropriate controls from the same laboratory, as well as side-to-side ratios. T2 relaxometry also quantitates hippocampal abnormalities and may show evidence of bilateral disease.²

Important note

Suboptimal MRI application in clinical practice
Current knowledge is still not being optimally applied in clinical practice.²⁶ For example, a recent study in Germany showed that, in patients with focal seizures who had unremarkable MRI scans at general hospitals, a focal lesion was found in 85% of cases when they later underwent MRI at a specialised centre.²⁷

X-ray CT scanning can detect gross structural lesions, but will miss many small mass lesions including tumours, vascular malformations, hippocampal sclerosis and most malformations of cortical development.² A negative CT scan conveys little information. For this reason CT should not be relied on and usually does not need to be performed when MRI is available. Occasionally CT may be useful as a complementary imaging technique in the detection of cortical calcifications, particularly in patients with congenital or acquired infections (e.g. cysticercosis) or tumours such as oligodendrogliomas.²

If MRI is not readily available or cannot be performed for technical reasons (e.g. a patient who has a cardiac pacemaker or a cochlear implant) then an X-ray CT scan is an appropriate initial investigation.

An X-ray CT scan is also useful in the acute situation of seizures developing in the context of a neurological insult such as head injury, intracranial haemorrhage or encephalitis, particularly if there is a need to have ready access to the patient during scanning.²

Conventional isotope brain scans do not provide sufficient information about the brain structure for identifying many lesions associated with seizures and their use is not recommended.²

Single photon emission computed tomography and positron emission tomography are also inadequate for assessment of the brain structure.²

Functional Neuroimaging in Clinical Practice ⁴

The Neuroimaging Subcommission of the ILAE has reassessed the roles of the traditional functional imaging techniques of PET and SPECT in clinical practice and research.⁴ The place of these methods and of the emerging magnetic resonance-based functional imaging methods of fMRI and magnetic resonance spectroscopy (MRS) also need to be considered in the light of the advances in structural imaging with MRI.

The Neuroimaging Subcommission of the ILAE⁴ considered fMRI, MRS, SPECT and PET in turn, according to the following format.

• Indications in clinical practice and research potential.
• Relation to structural imaging.
• Minimum and optimal standards if the investigation is to be carried out, with regard to equipment, clinical protocol and logistics, and reporting and interpretation.
• Misuse and pitfalls.

The conclusions regarding clinical applications of functional neuroimaging are as follows.⁴

Functional Magnetic Resonance Imaging

There is no currently approved or universally accepted clinical indication for fMRI.⁴ However, this situation is changing and in many epilepsy surgery centres fMRI is being used for localising the primary motor cortex and lateralising language function (Figure 3.7). Furthermore, continuous recording of an EEG and fMRI is now possible following the introduction of methods for removing the artefact on the EEG trace caused by the fMRI acquisition, resulting in much more detail and analysis of the time course of haemodynamic changes.^29–32 Clinically, these methods will aid EEG interpretation and understanding of the pathophysiological basis of epileptic activity.^15,30

Figure 3.7

fMRI scan showing an area of cerebral activation in relation to right-hand movement that is anterior to structural lesion (dysembryoplastic neuroepithelial tumour). Figure courtesy of Professor John S. Duncan and the National (more...)

Single Photon Emission Computed Tomography

SPECT with cerebral blood flow agents is useful for supporting the localisation of focal epilepsy when it is performed in a carefully monitored ictal (Figure 3.8) or early post-ictal examination compared with an inter-ictal scan. This may be used as part of pre-surgical evaluation and help to guide the placement of intracranial electrodes if other data including structural imaging are equivocal or non-concordant. In apparently generalised epilepsies, ictal SPECT may be helpful for identifying a focal component.⁴ Recent developments allow patients to inject the isotope themselves at the first warning of a seizure, thus increasing the possibility of capturing a seizure as well as reducing the interval between seizure onset and trapping of the tracer in the brain.³⁴

Figure 3.8

Ictal SPECT in a Child with Right Hippocampal Epilepsy. Coronal (top) and axial (bottom) 99Tc HMPAO SPECT images show increased perfusion in the right anterior temporal lobe (arrows). Figure courtesy of Dr Rod C. Scott, Institute of Child (more...)

Positron Emission Tomography with ¹⁸F Fluorodeoxyglucose (Fdg) and ¹⁵O Water (H₂ ¹⁵O)

Inter-ictal FDG-PET may have a role in determining the lateralisation of temporal lobe epilepsy, without intracranial EEG recording of seizures, in patients in whom there is not good concordance between MRI, an EEG and other data (Figure 3.9). This role has decreased with the wider availability of high-quality MRI. In patients with normal or equivocal MRI or discordance between MRI and other data, such that intracranial electrodes are required, FDG-PET may be useful for planning the sites of intracranial electrode placement for recording ictal onsets in temporal and extratemporal epilepsies. However, caution is needed as the ictal onset zone may be at the border of the hypometabolic area and not at the most hypometabolic area. FDG-PET may have a useful role in apparently generalised epilepsies in trying to define a focal abnormality and when resection may be contemplated. For practical purposes, the clinical and research uses of H₂ ¹⁵O PET for mapping areas of cerebral activation have been superseded by fMRI.⁴

Figure 3.9

Axial inter-ictal FDG-PET images in three patients with left mesial temporal sclerosis: all had a left anterior temporal lobectomy and became free of seizures. Left: Unilateral glucose hypometabolism in a 22-year-old male. FDG uptake is (more...)

Co-Registration of SPECT/PET with MRI

The co-registration of post-ictal SPECT images with a patient’s MRI improves the anatomical determination of abnormalities of the cerebral blood flow.³⁵ The objectivity and accuracy of data interpretation is enhanced with co-registration of inter-ictal with ictal or post-ictal SPECT images, resulting in an ‘ictal difference image’ that may be co-registered with the individual’s MRI. The co-registration of PET images with high-resolution MRI structural images from the same individual has practical value in the anatomical interpretation of functional abnormalities in PET with account been taken for potential partial volume artefacts. Together with an MRI image, PET images with different tracers, for example FDG and FMZ, can be co-registered, which enables a direct comparison of the location, pattern and extent of each abnormality (Figure 3.10).

Figure 3.10

Coronal (upper rows) and axial (lower rows) views of structural and functional neuroimages of a 21-year-old male with right mesial temporal sclerosis. A right anterior temporal lobectomy rendered him free of seizures. FDG-PET (more...)

Magnetoencephalography

Magnetoencephalography (MEG) is a promising but still in development non-invasive and non-hazardous technology of functional brain mapping.^36–45 It is used to identify both normal and abnormal brain function “in action”. MEG records externally from the scalp the weak magnetic forces associated with the electrical activity of the brain. It provides good spatial resolution of 2 mm and an excellent high temporal resolution on the order of 1 ms.

The primary advantage of MEG over EEG is that the magnetic fields are not altered by the skull and other surrounding brain structures, thus permitting greater accuracy owing to the minimal distortion of the signal. This allows for more usable and reliable localisation of brain function though MEG is better at detecting more superficially than deep mesial temporal lobe epileptogenic foci.

MEG is usually performed with simultaneous EEG recording. Superimposing MEG with X-ray CT and MRI scans produces functional/anatomic images of the brain, referred to as magnetic source imaging (MSI).

The most thoroughly studied clinical applications of MEG/MSI are to detect and localise (a) epileptogenic foci and (b) eloquent cortex.

The exact localisation of the epileptogenic area is crucial for screening of surgical candidates and surgical planning. MSI has principally been investigated as an alternative to invasive pre-surgical monitoring when clinical, EEG and MRI findings are not concordant. Additionally, in patients who have had past brain surgery, the electrical field measured by EEG may be distorted by the changes in the scalp and brain anatomy. If further surgery is needed, MEG may be able to provide the necessary information without invasive EEG studies.

Localisation of the “eloquent” brain areas such as sensorimotor regions is critical for their preservation during any type of brain surgery. MEG/MSI are used to map the exact location of the normally functioning areas near the lesion that should be avoided in planning surgical resection thus minimising postoperative significant neurological deficits. Such use might also obviate the need for other forms of invasive mapping techniques.

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