Structural magnetic resonance imaging (MRI) is of fundamental importance to the diagnosis and treatment of epilepsy, particularly when surgery is being considered. Despite previous recommendations and guidelines, practices for the use of MRI are variable worldwide and may not harness the full potential of recent technological advances for the benefit of people with epilepsy. The International League Against Epilepsy Diagnostic Methods Commission has thus charged the 2013‐2017 Neuroimaging Task Force to develop a set of recommendations addressing the following questions: (1) Who should have an MRI? (2) What are the minimum requirements for an MRI epilepsy protocol? (3) How should magnetic resonance (MR) images be evaluated? (4) How to optimize lesion detection? These recommendations target clinicians in established epilepsy centers and neurologists in general/district hospitals. They endorse routine structural imaging in new onset generalized and focal epilepsy alike and describe the range of situations when detailed assessment is indicated. The Neuroimaging Task Force identified a set of sequences, with three‐dimensional acquisitions at its core, the harmonized neuroimaging of epilepsy structural sequences—HARNESS‐MRI protocol. As these sequences are available on most MR scanners, the HARNESS‐MRI protocol is generalizable, regardless of the clinical setting and country. The Neuroimaging Task Force also endorses the use of computer‐aided image postprocessing methods to provide an objective account of an individual's brain anatomy and pathology. By discussing the breadth and depth of scope of MRI, this report emphasizes the unique role of this noninvasive investigation in the care of people with epilepsy.

Seizures are often followed by sensory, cognitive or motor impairments during the postictal phase that show striking similarity to transient hypoxic/ischemic attacks. Here we show that seizures result in a severe hypoxic attack confined to the postictal period. We measured brain oxygenation in localized areas from freely-moving rodents and discovered a severe hypoxic event (pO2 < 10 mmHg) after the termination of seizures. This event lasted over an hour, is mediated by hypoperfusion, generalizes to people with epilepsy, and is attenuated by inhibiting cyclooxygenase-2 or L-type calcium channels. Using inhibitors of these targets we separated the seizure from the resulting severe hypoxia and show that structure specific postictal memory and behavioral impairments are the consequence of this severe hypoperfusion/hypoxic event. Thus, epilepsy is much more than a disease hallmarked by seizures, since the occurrence of postictal hypoperfusion/hypoxia results in a separate set of neurological consequences that are currently not being treated and are preventable.DOI: http://dx.doi.org/10.7554/eLife.19352.001

Thirst was induced by rapid i.v. infusion of hypertonic saline (0.51 M at 13.4 ml͞min). Ten humans were neuroimaged by positron-emission tomography (PET) and four by functional MRI (fMRI). PET images were made 25 min after beginning infusion, when the sensation of thirst began to enter the stream of consciousness. The fMRI images were made when the maximum rate of increase of thirst occurred. The PET results showed regional cerebral blood flow changes similar to those delineated when thirst was maximal. These loci involved the phylogenetically ancient areas of the brain. fMRI showed activation in the anterior wall of the third ventricle, an area that is key in the genesis of thirst but is not an area revealed by PET imaging. Thus, this region plays as major a role in thirst for humans as for animals. Strong activations in the brain with fMRI included the anterior cingulate, parahippocampal gyrus, inferior and middle frontal gyri, insula, and cerebellum. When the subjects drank water to satiation, thirst declined immediately to baseline. A precipitate decline in intensity of activation signal occurred in the anterior cingulate area (Brodmann area 32) putatively related to consciousness of thirst. The intensity of activation in the anterior wall of the third ventricle was essentially unchanged, which is consistent with the fact that a significant time (15-20 min) would be needed before plasma Na concentration changed as a result of water absorption from the gut.

The mechanisms underlying the transition from interictal to ictal states are poorly understood. Non-linear mathematical analysis of EEG frequency components has confirmed the presence of a pre-ictal state in focal epilepsy. We report on functional MRI (fMRI) analysis of the pre-ictal state in three patients with intractable focal epilepsy. Each subject had a typical partial seizure in the scanner while continuous blood oxygen level dependent (BOLD) fMRI images were acquired. The pre-ictal BOLD changes were first analysed by statistically comparing BOLD signals of two one-minute blocks. Further examination of the full time course was then performed. Each patient showed highly significant, focal BOLD signal changes. In Patient 1, a striking pre-ictal BOLD signal increase was seen over the region of the seizure focus identified on complementary epilepsy investigations. No significant BOLD signal decreases were observed. Patient 2 showed widespread pre-ictal BOLD increase contralateral to the presumed seizure focus, as well as a focal BOLD decrease near the presumed seizure focus. In Patient 3, pre-ictal BOLD increase was co-localized with the site of hyperperfusion seen on ictal single photon emission computed tomography (SPECT). However, this was contralateral to the seizure focus localization based on seizure symptomatology. No significant BOLD decreases were seen. The time course data in each patient studied showed change of the BOLD signal several minutes before the onset of the seizure. Highly significant BOLD fMRI signal changes occur before the onset of seizures, supporting the presence of a pre-ictal state. These changes can be localized to the site of the presumed seizure focus, as well as to other brain regions, suggesting that the pre-ictal BOLD signal changes and their underlying mechanisms are complex.

A recent article by Farrell et al. characterizes the phenomenon, mechanisms, and treatment of a local and severe hypoperfusion/hypoxia event that occurs in brain regions following a focal seizure. Given the well-established role of cerebral ischemia/hypoxia in brain damage and behavioral dysfunction in other clinical settings (e.g., stroke, cerebral vasospasm), we put forward a new theory: postictal hypoperfusion/hypoxia is responsible for the negative consequences associated with seizures. Fortunately, inhibition of two separate molecular targets, cyclooxygenase-2 (COX-2) and l-type calcium channels, can prevent the expression of postictal hypoperfusion/hypoxia. These inhibitors are important experimental tools used to separate the seizure from the resulting hypoperfusion/hypoxia and can allow researchers to address the contribution of this phenomenon to negative outcomes associated with seizures. Herein we address the implications of this postictal stroke-like event in acute behavioral dysfunction (e.g., Todd's paresis) and sudden unexpected death in epilepsy (SUDEP). Moreover, anatomic alterations such as increased blood-brain barrier permeability, glial activation, central inflammation, and neuronal loss could also be a consequence of repeated hypoperfusion/hypoxic events and, in turn, underlie chronic interictal cognitive and behavioral comorbidities (e.g., memory deficits, anxiety, depression, and psychosis) and exacerbate epileptogenesis. Thus these seemingly disparate and clinically important observations may share a common point of origin: postictal hypoperfusion/hypoxia.