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  • Updated 04.09.2021
  • Expires For CME 04.09.2024

Neuroimaging of epilepsy

Introduction

Overview

Neuroimaging plays a critical role in the diagnosis and treatment of adult and pediatric epilepsy. The following article details the indications for neuroimaging in patients with epilepsy and explains how neuroimaging contributes to the surgical planning for medication-resistant epilepsy. This includes discussion of structural and diffusion MRI, functional MRI, positron emission tomography, single-photon emission computerized tomography and magnetoencephalography. Automated quantitative processing of neuroimages is discussed even though these methods of analysis have not yet been validated enough to become standard-of-care. The limited role of computed tomography also is discussed.

Key points

• All patients with medication-resistant seizures should undergo an MRI, provided that there are no contraindications.

• The goal of neuroimaging in epilepsy is to identify structural or functional abnormalities that are associated with the clinically observed ictal behavior.

• Concordance of multimodal neurodiagnostic information, including ictal behavior, EEG, and neuroimaging, is necessary to localize the likely epileptogenic region.

• The role of x-ray, CT, and angiography is limited in unprovoked seizures not associated with vascular abnormalities.

Historical note and terminology

In this article, we focus on neuroimaging in adult epilepsy and present some cases that also apply to pediatrics. Epilepsy is defined as an enduring predisposition for unprovoked seizures caused by abnormally synchronous epileptiform neural activity (25). To be diagnosed with epilepsy, a patient must have had either (1) two unprovoked seizures, (2) one unprovoked seizure and neuroimaging evidence of a greater than 60% chance of continued seizures (discussed below), or (3) an epilepsy syndrome (15). The neuroimaging of provoked seizures is a separate topic. Further, the depth and breadth of neuroimaging findings and epilepsy syndromes of pediatric epilepsy preclude a concise discussion of both adult and pediatric epilepsy within the same topic. Similarly, discussion of the central role of electroencephalography in seizures is a separate topic.

The characterization of epilepsy is based on localization of the onset and spread of epileptiform activity that cause the ictal behavior. The nomenclature of epilepsy has been revised to respect this focus on localization. Seizures are classified as either focal-onset with or without loss of awareness; or generalized-onset, formerly referred to as simple or complex partial; or grand mal (15). In addition, we define the following subtly different terms to more accurately describe the role of neuroimaging in localization of seizures and their onset (36):

• Epileptogenic lesion: a radiographically apparent abnormality that may be associated with the underlying etiology of the epileptic seizures.

• Epileptogenic zone: the region of cortex that is necessary and sufficient for the generation of epileptic seizures.

• Seizure-onset zone: the region of cortex where the epileptiform activity is first evident.

• Irritative zone: the region of cortex that generates interictal epileptiform abnormality.

• Symptomatogenic zone: the region of cortex that generates the externally observed ictal behavior of epilepsy.

• Functional deficit zone: the region of cortex that exhibits interictal abnormal function.

• Eloquent cortex: regions of cortex that are related to functions that, if lost, would result in unacceptable deficits.

• Nonlesional epilepsy: a person with epilepsy that has no abnormal neuroimaging findings that could be associated with the underlying etiology of epileptic seizures. Sometimes nonlesional refers specifically to MRI-negative epilepsy without consideration of other neuroimaging modalities.

Vollmar and Noachtar published an illustrative figure to describe the overlapping relationship between each of these zones and the information modalities used to define them (49).

The goal of resective or ablative surgery for epilepsy is to remove the epileptogenic zone while sparing eloquent cortex. Neurodiagnostic testing can provide information about the various other zones and lesions, from which we infer the epileptogenic zone. However, the epileptogenic zone can only be confirmed retrospectively by removing or ablating a region of cortex that contains the epileptogenic zone.

The development of imaging techniques to visualize the anatomy and pathophysiology of intracranial processes has been critical to our improved understanding of the causes of seizures. In the 1930s, skull x-rays and angiograms identified aneurysms, intracranial calcifications, developmental malformations, boney lesions, and trauma that could provide indirect evidence of potential epileptogenic lesions (29). The development of tomographic imaging in the 1970s made it possible to visualize aspects of the structure of intracranial contents through x-ray CT. This made it possible to identify more subtle epileptogenic lesions including tumors, calcifications, and gross malformations (16). The combination of tomographic imaging with radioactive tracers allowed for the visualization of neural functions through PET and SPECT. FDG-PET visualized the functional deficit zone by providing quantitative evidence of interictal hypometabolism of glucose ipsilateral to the seizure-onset zone in mesial temporal lobe epilepsy (Engel et al 1982; 41). Similarly, when radiotracer is injected within seconds of the beginning of seizures, regions of hypermetabolism measured by SPECT can identify the seizure-onset zone.

The field of neuroimaging in epilepsy was revolutionized MRI and its ability to visualize soft tissue and, specifically, mesial temporal sclerosis associated with mesial temporal lobe epilepsy (24). As imaging techniques in MRI advanced and acquisition times decreased, MRI became able to quantify blood-oxygen-level dependent (BOLD) signal that was associated with eloquent neural activity. Although diffusion MRI plays a key role in ischemic stroke (48), its diagnostic role in epilepsy is limited.

With the various methods of analyzing the structural and functional aspects of each individual’s epilepsy, the goal is to integrate each of these clinical, neurophysiological, and neuroimaging findings into a comprehensive understanding of the patient’s epilepsy.

Localization of epileptic seizures in brain

Alternative Venn diagram of localization of epileptic seizures including subtle differences between each of the neurodiagnostic modalities, both within modalities and across modalities. (Image from: Tamilia E, Madsen JR, Grant ...

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