Images 8.1A–8.1C: Coronal T2-weighted and coronal and axial FLAIR images demonstrate hyperintensity and atrophy of the right hippocampus (red arrow). Mild enlargement of the temporal horn is noted. Image 8.1D: Pathological demonstration of hippocampal sclerosis (image courtesy of Dr. Seema Shroff, Fellow, Neuropathology, NYULMC).

Introduction

  A seizure is defined by the International League Against Epilepsy (ILAE) as “abnormal excessive or synchronous neuronal activity in the brain.” Epilepsy is defined as recurrent, unprovoked seizures due to inherent neuronal hyperexcitability. Seizures can be provoked or unprovoked. Examples of provoked seizures include metabolic derangements, such as hyponatremia, drug withdrawal (alcohol and benzodiazepines being the most common), or drug intoxication.

  The lifetime risk of epilepsy is about 3% and about 10% of adults will have a seizure at some point in their lives. The rate of epilepsy is high in early childhood (ages 0–14.) In children, genetic factors, congenital malformations, trauma, and neoplasms are the cause of most seizures. The risk of epilepsy declines significantly until the age of 60, at which vascular disease, neoplasms, trauma, infections, and neurodegenerative disorders are responsible for most seizures. In this age group, vascular disease is the leading cause of seizures, accounting for over 50%.

  There are two broad classifications of epilepsy: focal and generalized seizures.

Focal Seizures

  Focal seizures are those that have their onset at a specific brain location due to some localized pathology of the cerebral cortex. These may be related to some focal brain lesion such as an infection, tumor, or injury, though in most cases the cause is unknown. Partial seizures are further divided into simple and complex seizures, depending on whether or not a patient’s consciousness is impaired. A simple partial seizure does not affect consciousness. Partial seizures may manifest with motor, sensory, autonomic, or psychiatric symptoms, often a sense of overwhelming fear or depersonalization. Complex partial seizures affect consciousness and are most commonly associated with abnormalities of the medial temporal lobe. Simple partial seizures may spread and evolve into complex partial seizures. They may further spread throughout the entire brain, in which case they are called secondarily generalized seizures. An aura (warning) is an abnormal sensation that may precede a partial seizure.

Generalized Seizures

  Primary generalized seizures involve both cerebral hemispheres at once without a localized area of onset. The etiology of these seizures is often hereditary. Auras do not occur in primarily generalized seizures. Generalized seizures, whether primary or secondary, always involve the impairment of consciousness, even if only for a few seconds. Types of primary generalized seizures include:

          Absence seizures: Absence seizures are divided into typical and atypical forms. Typical absence seizures are characterized by brief (less than 10 seconds) episodes of unresponsiveness after which patients rapidly return to baseline, often unaware that they had a seizure. There may be subtle eye-blinking or facial movements. These seizures can be provoked by hyperventilation or photic stimulation. Atypical absence seizures are longer (up to 30 seconds) with more pronounced motor movements, and postictal confusion.

          Myoclonic seizures: Myoclonic seizures are characterized by rapid, “shock-like” jerks of individual muscles or the entire body.

          Tonic–clonic seizures: In the tonic phase of the seizure, the patient abruptly loses consciousness followed by a loud vocalization (the epileptic cry) as air is expelled from the lungs against a close glottis. The skeletal muscles tense and the patient falls to the ground if standing. After 10 to 30 seconds, the clonic phase begins. It is characterized by dramatic muscle contraction and relaxation of progressively increasing duration. Patients may bite their tongues due to contracture of the jaw muscles, and the eyes are open in almost all cases. There are increases in heart rate, blood pressure, pupillary dilation, and salivation. The entire seizure lasts 1 to 3 minutes. Patients are often confused after the seizure, and in some cases may become frankly psychotic, a state termed postictal psychosis. Bowel and bladder incontinence are common in the postictal phase. Todd’s paralysis refers to motor weakness that persists after a seizure, sometimes as long as 24 hours. Patients may exhibit persistent symptoms other than weakness, such as aphasia, though this is less common. This is the most common type of seizure, experienced by about 10% of patients with epilepsy.

          Clonic seizures: Clonic seizures are similar to tonic seizures, but without the tonic component. They usually start before the age of 3.

          Tonic seizures: Tonic seizures are characterized by tonic spasms of the facial and truncal muscles, with flexion or extension of the extremities. The patient often falls to the ground, and serious injury may result. These seizures usually being in early childhood.

          Atonic seizures: Atonic seizures, also known as drop attacks, are characterized by the sudden weakness of postural muscles. They can be mild and result in a mere head drop, or severe and result in a complete loss of postural tone and severe injuries.

  The localized and generalized categories are divided into three further categories: idiopathic (unknown or inherited cause), symptomatic (identifiable cause), and cryptogenic (brain lesion is suspected, but cannot be identified).

  Another method of classifying seizures is by dividing them into epilepsy syndromes as defined by the ILAE. Epilepsy syndromes are defined by a cluster of features including the type of seizure, its localization, frequency, precipitating factors, age at onset, additional features of neurological or systemic disease, genetic factors, prognosis, and suggested treatments.

          West syndrome: West syndrome occurs in children aged 3 months to 2 years, most commonly in infants aged 8 to 9 months. It is defined by the triad of mental retardation, seizures known as infantile spasms (IS), and a pathognomonic EEG pattern (high-amplitude waves and a background of irregular spikes) called hypsarrhythmia. The most common cause is tuberous sclerosis, though it may be idiopathic. The prognosis is related to the underlying cause, though most children have significant cognitive disability and other seizures, including Lennox–Gastaut syndrome (LGS). It is treated with adrenocorticotropic hormone (ACTH) and conventional antiepileptic drugs (AEDs).

          Lennox–Gastaut syndrome: LGS develops in children aged 2 to 18 years old. It is characterized by a variety of generalized seizures (astatic seizures [drop attacks], tonic seizures, tonic–clonic seizures, atypical absence seizures, and less frequently, complex partial seizures) and developmental delay. The characteristic EEG shows slow spike-wave complexes of 2 Hz. AEDs are rarely effective in stopping the seizures.

          Juvenile myoclonic epilepsy: Juvenile myoclonic epilepsy (JME) is a primarily generalized epilepsy that develops in teenagers and young adults who are otherwise healthy and without neurological deficits. As the name implies, patients most often experience myoclonic jerks, though other seizure types occur as well. The jerks are most common early in the morning, and patients are often thought to “be clumsy.”The EEG has a characteristic pattern, showing generalized 4 to 6 Hz spike-wave discharges or multiple spike discharges. They are triggered by sleep deprivation, and a classic presentation is that of a teenager who has a generalized seizure after staying up all night. Patients will need lifelong treatment with AEDs, and avoidance of triggers, namely sleep deprivation.

          Benign centrotemporal epilepsy of childhood: Benign centrotemporal epilepsy of childhood (also known as benign Rolandic epilepsy) occurs in otherwise healthy children 3 to 13 years old. The seizures almost always occur at night and the most common type of seizure is a partial seizure involving the facial muscles. Speech arrest and drooling are common. For such seizures, no treatment is required, and the seizures always remit during puberty. In some circumstances, the seizures may generalize and AEDs may be required in such children. The characteristic EEG shows epileptic spike discharges originating from the centrotemporal scalp over the central sulcus (the Rolandic sulcus), which most commonly occur during the early stages of sleep.

          Benign occipital epilepsy of childhood: Benign occipital epilepsy of childhood (BOEC) occurs in children younger than 10 and is characterized by seizures on one half of the body and a variety of visual distortions including loss of vision or positive visual phenomena typically described in migraines, such as scintillating scotomas or brightly colored patterns or shapes (fortification spectra). As in migraines, headaches and nausea are common. The EEG reveals spikes originating from the occipital lobes.

          Landau–Kleffner syndrome: Landau–Kleffner syndrome (also known as acquired epileptic aphasia) is characterized by seizures and a progressive aphasia. It usually starts as a receptive aphasia, but may eventually develop into a global aphasia or even a complete auditory agnosia. It occurs in children between the ages of 5 and 7 who were previously healthy. Spontaneous remission may occur.

          Progressive myoclonic epilepsies: The progressive myoclonic epilepsies (PMEs) are a collection of disorders characterized by progressive cognitive decline and seizures. Myoclonic seizures are the most common, though tonic–clonic seizures may occur. Specific examples of PMEs include Unverricht–Lundborg disease (Baltic myoclonus); myoclonus epilepsy and ragged red fibers (MERRF); Lafora disease; neuronal ceroid lipofuscinosis; and type I Sialidosis. The most common of these is Unverricht–Lundborg disease, which occurs in children between ages 6 and 15. It is an autosomal-recessive inherited disorder that begins in children aged 6 to 18 with seizures and cognitive decline over the course of several decades. MERRF is a mitochondrial disorder characterized by both myoclonic and generalized tonic–clonic seizures (GTCs). Other features include developmental delay, deafness, and exercise intolerance.

          Febrile seizures: Febrile seizures occur in children aged 6 months to 6 years when there is a rapid rise in temperature. Boys are affected at twice the rate of girls. A simple febrile seizure is a generalized seizure that lasts less than 15 minutes (usually much less) and does not recur in a 24-hour period. In contrast, any seizure that is partial in onset, lasts for more than 15 minutes, or recurs in a 24-hour period is termed a complex febrile seizure. Risk factors for developing seizures later in life include complex partial seizures, an abnormal neurological exam, or nonfebrile seizures in a first degree relative. For most children, no treatment is required. Technically, febrile seizures are classified as a seizure condition that does not require the diagnosis of epilepsy.

          Reflex seizures: Reflex seizures are those which are triggered in response to a sensory stimulus. The stimuli are most commonly visual and include television and video games. Other stimuli known to cause seizures include reading and the startle response. Most seizures are generalized tonic–clonic.

          Symptomatic localization-related epilepsies: Symptomatic localization-related epilepsies are defined by the lobe of the brain in which the seizure originates. Epilepsies arising from lobes of the brain, other than the medial temporal lobes, are often due to tumors, infarcts, vascular malformations, traumatic injuries, or infectious processes such as neurocysticercosis. It is important to note that any lesion must affect the cerebral cortex in order to cause a seizure, and lesions of the white matter, basal ganglia, thalamus, and brainstem are not associated with seizures. Patients with seizures arising from the frontal lobes often have bizarre, seemingly purposeful motor behaviors that are often mistaken for nonepileptic seizures.

Clinical Presentation

  Temporal lobe epilepsy (TLE) is a specific type of complex partial seizure, which as the name implies, arises from the medial temporal lobes. Though this is the most common origin of the focal epilepsies, other lobes of the brain can serve as seizure foci as well. The medial temporal lobe contains several important structures, namely the hippocampus, the amygdala, and the olfactory cortex. These structures are an integral part of the limbic system.

  The clinical features of the aura in patients with TLE reflect the anatomy of the medial temporal lobe. Déjà vu is a feeling of increased familiarity reflecting seizure activity in the hippocampus. Some patients experience the opposite, jamais vu, where familiar situations suddenly seem unrecognizable. Patients may also experience a strong feeling of fear due to activation of the amygdala, and patients may experience unpleasant odors, often described as if something is burning.

  Patients with TLE typically have a preceding aura, which can be:

          Somatosensory and special sensory: epigastric sensations or rising surge, metallic taste in mouth, strange smell, vertigo, visual, hearing

          Psychic: déjà vu (recalled emotions or memories), jamais vu (feelings of unfamiliarity), sudden intense emotions, depersonalization and derealization, extreme fear, anxiety

          Autonomic: abdominal pain, dilated eyes, sweating, piloerection, flushed face, nausea, palpitations, profuse salivation (slobbering), changes in heart rate

  Automatisms are also common in temporal lobe seizures. There can be oro-masticatory manual/pedalor reactive automatisms.

  Motionless stare, behavioral arrest, speech arrest, unilateral dystonic posturing, periods of confusion, disorientation, and decreased responsiveness are common clinical features seen during dyscognitive seizures.

Radiographic Appearance and Diagnosis

  The MRI with epilepsy protocol includes T1-inversion prepared, gradient echo, echoplanar, true inversion recovery image, T2-fast spin echo, fluid-attenuated inversion recovery (FLAIR), and 3D volume acquisition of thin temporal cuts. The most common identifiable lesion on the brain MRI is mesial temporal sclerosis (MTS). In patients with TLE, subtle anatomic features of the medial temporal lobes and pathologies like MTS or incomplete hippocampal inversion are best appreciated in an oblique coronal plane. This orientation is orthogonal to the long axis of the temporal lobe and reduces volume averaging problems for the thin laminar appearance of the hippocampus. Oblique coronal temporal high-resolution T2-weighted and FLAIR are the best sequences to diagnose MTS.

  MTS is characterized by hippocampal atrophy, increased T2 signal, and abnormal morphology or loss of internal architecture of hippocampus. In 10% of the cases, MTS can be bilateral.

  Secondary findings may include dilatation of the temporal horn of the lateral ventricle, loss of gray–white matter differentiation in the temporal lobe, or decreased white matter in the adjacent temporal lobe (eg, collateral eminence and temporal stem). There can be atrophy of the ipsilateral fornix and mammillary body. High-resolution 3D T1-weighted images are also useful when performing hippocampal volumetric analyses.

AVM, arteriovenous malformation; DTI, diffusion tensor imaging; DWI, diffusion-weighted image; FDG-PET, fludeoxyglucose-PET; fMRI, functional magnetic resonance imaging; MEG, magnetoencephalogram; MRS, magnetic resonance spectroscopy; MSI, magnetic source imaging; NAA, N-acetyl aspartate; NAA/Cho, NAA/Choline; NAA/Cr, NAA/Creatine; SISCOM, subtraction ictal SPECT co-registered to MRI; SPECT, single photon emission computed tomography; VEEG, video EEG.

  Status epilepticus (SE) is a life-threatening condition defined as a seizure lasting longer than 30 minutes, or recurrent seizures without regaining consciousness between seizures for greater than 30 minutes. Benzodiazepines are the preferred initial management due to their rapid onset of action. Note that intravenous (IV) phenytoin cannot be given rapidly due to its risk for cardiac arrhythmias. Fosphenytoin can be given at triple the rate of phenytoin and can be given intramuscularly. The MRI findings for a patient who was in SE are shown.

Images 8.1E and 8.1F: Coronal FLAIR and axial diffusion-weighted images demonstrate hyperintensity and multiple areas of restricted diffusion, primarily in the cortical ribbon of the right hemisphere.

  Epilepsia partialis continua refers to a persistent focal motor seizure, typically involving the hand, foot, or face.

Image 8.1G: Axial FLAIR image demonstrates hyperintensity of the right medial temporal lobe.

Image 8.1H: Axial T2-weighted image demonstrates intracranial electrodes used to determine the seizure focus.

Image 8.1I: Axial T2-weighted image demonstrates postoperative changes after a partial right temporal lobectomy.

  In patients for whom cortical areas cannot be removed without potentially devastating neurological impairment, a surgical technique known as multiple subpial transections is used to prevent seizure spread. It involves making a number of small incisions into the cerebral cortex with the hopes of disrupting epileptic circuits in the brain without impairing the function of the brain areas. This technique is most commonly employed in seizures that originate in brain areas responsible for language or motor function, which cannot be removed without significant neurological impairment. This surgical procedure is useful in seizure syndromes such as Landau–Kleffner syndrome, where surgery cannot be performed without potentially devastating the patient.

  In some patients with epilepsy refractory to medications, surgical lesions can be made in the corpus callosum to prevent seizures spreading from one hemisphere to the other. It is used almost exclusively in patients with generalized epilepsy with drop attacks.

  Vagus nerve stimulation involves implanting an electrode on the midcervical portion of the vagus nerve, which then sends intermittent electrical impulses through the nerve. VNS is recommended in patients with bilateral temporal seizure foci.

Images 8.1J and 8.1K: Axial and sagittal T1-weighted images demonstrate anterior corpus callosotomy (red arrows).

References

1.  Proposal for revised classification of epilepsies and epileptic syndromes. Commission on classification and terminology of the International League Against Epilepsy. Epilepsia. 1989;30:389.

2.  Berg AT, Berkovic SF, BrodieMJ, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005–2009. Epilepsia. 2010;51:676.

3.  Abosch A, Bernasconi N, Boling W. Factors predictive of suboptimal seizure control following selective amygdalohippocampectomy. J Neurosurg. 2002;97(5):1142–1151.

4.  Engel J Jr, McDermott MP, Wiebe S, et al. Early surgical therapy for drug-resistant temporal lobe epilepsy: a randomized trial. JAMA. March 2012;307(9):922–930.