CME

Approach to Seizures, Epilepsies, and Epilepsy Syndromes

Martina Vendrame, MD, PhD ^a, Tobias Loddenkemper, MD ^b^,^*

^a Division of Clinical Neurophysiology and Sleep, Department of Neurology, Boston University, Neurology C-3, 72 East Concord Street, Boston, MA 02118, USA

^b Division of Epilepsy and Clinical Neurophysiology, Children’s Hospital Boston, Harvard Medical School, Fegan 9, 300 Longwood Avenue, Boston, MA 02115, USA

^* Corresponding author.

E-mail address: tobias.loddenkemper@childrens.harvard.edu

Abstract

Seizures and epilepsies present with multiple causes and multiple clinical features, and change across the lifespan. Epilepsy is not a single disease but a diverse group of disorders that have in common an abnormally increased predisposition to epileptic seizures. A systematic approach to epileptic seizures and epilepsies is a first step toward the diagnosis and treatment of these disorders. Description of findings is crucial for selection of the most helpful diagnostic and therapeutic approach, defining relationships to sleep and sleep-related interactions, and comorbidities.

Keywords

• Epilepsy syndromes • Classification • Semiology of seizures

Seizures and epilepsies present with multiple etiologies and multiple clinical features and change across the lifespan. Epilepsy is not a single disease but a diverse group of disorders that have in common an abnormally increased predisposition to epileptic seizures. A systematic approach to epileptic seizures and epilepsies is a first step toward the diagnosis and treatment of these disorders. Determination of clinical seizure type, epilepsy localization, underlying etiology, related medical conditions, and, if possible, epilepsy syndrome follows the general neurologic approach in clinical practice, including description of symptomatic presentation, localization, and etiologic investigation. Description of findings is crucial for selection of the most helpful diagnostic and therapeutic approach, defining relationships to sleep and sleep-related interactions, and comorbidities. For the purposes of this article, the following definitions are used:

Seizure refers to a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.¹ Elements defining an epileptic seizure include mode of onset and termination, clinical manifestations, and abnormal enhanced synchrony.¹

Epilepsy is a condition characterized by ¹ (1) recurrent (2 or more) epileptic seizures, unprovoked by any immediate identified cause; (2) multiple seizures occurring in a 24-hour period that are considered a single event; and (3) an episode of status epilepticus that is considered a single event. Individuals who have had only febrile seizures are excluded from this category.

Epilepsy syndrome refers to a complex of signs and symptoms that define a unique epilepsy condition. This must involve more than just the seizure type; thus, frontal lobe seizures by themselves, for instance, do not constitute a syndrome.²

Diagnostic approach

The diagnostic approach to seizures and epilepsy involves 4 independent steps as follows.³ These steps have been implemented in the most recent suggestion for a revised epilepsy classification.⁴

1. Clinical presentation (What are the symptoms?)

2. Epilepsy localization (Where is the lesion?)

3. Etiology (What is causing the epilepsy?)

4. Syndrome (other related features that may assist with diagnosis making or fit with known syndromes).

Independent investigational techniques include the collection of a detailed history and clinical course; seizure semiology analysis either by history or video review; physical examination; electrophysiologic studies; structural neuroimaging and functional and metabolic neuroimaging; and laboratory testing, including genetic and histopathologic studies; these studies aid in answering the questions outlined previously.

Recognizing Nonepileptic Events

When gathering information on events, always consider the option that events may be nonepileptic. In general, when witnesses report the ability to modify or stop a patient’s ictal movements during an epileptic seizure, a nonepileptic event should be considered.⁵ In Box 1 some clinical features that may aid the characterization of nonepileptic events, such as psychogenic seizures, parasomnias, and nocturnal panic attacks, are summarized.

Box 1 Clinical features that may suggest nonepileptic events

Convulsive Psychogenic Nonepileptic Event

• Less stereotyped

• Does not follow an orderly sequence of a epileptic convulsion

• Long duration (most epileptic convulsions last less than 1–2 minutes; PNES convulsions often last 5–20 minutes or longer)

• Motor movements often are arrhythmic, are asynchronous, and stop then start again

• Eyes closed (eyes usually open with an epileptic convulsion)

• Seems to voluntarily modify or stop movements during the event

• Little or no postictal confusion

• Postictal crying, whispering

• May recall fragments, if gently pressed, with some responsiveness or recall of ictus

NREM Arousal Parasomnias

• 1–2 Episodes per night

• 1–4 Episodes per month

• Episodes occur during NREM 3 sleep

• Episodes occur more likely after 90 minutes of sleep onset

• Episodes can last up to 30 minutes

• Variable movements and actions (less stereotyped)

• Physical and verbal interaction can be seen

• Failure to arouse after the event

• Positive family history is common

Sleep-Related Panic Attacks

• 1–2 Episodes per night

• Episodes lasts 2–8 minutes

• Affective and autonomic features may be predominant

• The patient is aware during the event

• The patient recognizes the event as a panic attack and has a vivid recall

• History of daytime panic attacks is usually present

• Episodes usually occur during transition from NREM 2 to NREM 3

Abbreviations: NREM, non–rapid eye movements of sleep; PNES, psychogenic nonepileptic seizures; SWS, slow wave sleep.

The distinction between epileptic and nonepileptic events may represent a significant challenge for clinicians. The most commonly encountered nonepileptic events are the so-called PNES.⁶ It is estimated that approximately 70% of PNES cases develop between the second and fourth decades of life, but PNES can also present in children and senior individuals.⁶ Patients with PNES may have concurrent epileptic seizures or have had epileptic seizures before presenting with PNES.⁶

Some clinical features can help differentiate PNES from epileptic seizures, but most features are highly nonspecific and no single feature is pathognomonic for PNES.^5,⁷ When events occur during the night, and out of sleep, this distinction may be even more difficult. Disorders that may present with nocturnal nonepileptic paroxysmal events may include (1) specific sleep-related disorders, such as NREM 3 parasomnias and rapid eye movement (REM) sleep behavior disorder, and (2) psychiatric and behavioral conditions, such as panic attacks⁸^–¹⁰ or PNES, among others. These phenomena usually involve complex motor activity as seen in parasomnias and may have a wide spectrum of alterations of consciousness/awareness, which makes their differentiation from seizures difficult.

An abrupt onset is typically more suggestive of epileptic seizures, although other events, such as cardiac or vasovagal syncope, can also present with rapid onset. Epileptic seizures tend to have a stereotypical pattern, which means that witnesses and patients tend to report events with similar dynamics and features. At times, more than one type of event can be recognized by witnesses/patients and clinician. Ictal activity is also involuntary and uncontrollable, which means that during the seizure the behavior is not goal directed. Some patients during complex partial seizures (especially right temporal in origin) can follow commands often then accompanied by automatisms and varying degrees of amnesia. At times, behavior in response to an ictal aura can be seen, which is primarily not ictal in nature but related to the epileptic seizure, such as hand shaking due to a painful aura in the hand. Postictal alterations, including amnesia for the event, lethargy/sleep, and transient neurologic deficits, are also more likely in epileptic seizures and are typically reported with consistency by family members and caretakers.

When typical seizures can be recorded, video-electroencephalogram (EEG) is the gold standard diagnostic tool for nonepileptic events, and a diagnosis of these disorders can be made with high accuracy.^6,¹¹ When video-EEG reveals no ictal epileptic activity before, during, or after the ictus, thorough neurologic, sleep, and psychiatric histories are crucial to confirm the diagnosis of these disorders.

Seizure History and Semiology

Identification and classification of seizures and epilepsies is based on clinical presentation. In epilepsy, semiology refers to the study of the signs and symptoms of seizures. The seizure semiology provides important clues to seizure and epilepsy localization. The collection of information on seizure history and semiology, together with the analysis of seizure semiology with video-EEG data, is essential for understanding the clinical seizure type and provides important information on the type of epilepsy and localization, guiding treatment and addressing prognosis. Furthermore, semiology provides important lateralizing and/or localizing information.¹²^–¹⁴

The authors find it most useful to analyze the main phases of a seizure along the timeline of occurrence.¹⁵ Simply imagine the timeline of a seizure, and inquire of features in this timeline separately, specifically

1. Seizure setting

2. Seizure onset

3. Seizure presentation and evolution and

4. Postictal symptoms.

Seizure setting

Information on seizure setting requires a reliable witness capable of accurately describing the details of the entire event. If a patient is amnestic for all or part of the seizure, an independent witness is crucial. Circumstances immediately prior to the event should be noted, such as the activity in which the patient was engaged, changes in the environment, changes in the patient’s behavior before seizure onset, and other prodrome (ie, the symptoms reported within minutes, hours, or even days before the seizure onset). The time of day and relationship of the events to sleep may also be elicited. For example, knowing that the events have a specific circadian pattern, arise from a particular sleep/wake state, or occur in the context of sleep deprivation helps distinguish different seizure types and epilepsy syndromes.¹⁶^–¹⁸ The presence of fever, concomitant illness, occurrence in high-altitude settings, preceding head injury, and perimenstrual timing may be helpful.¹⁹ Information of seizure setting includes also prior medical history, current medical health, cognitive deficits, developmental achievements, and family history.

Seizure onset

Seizure onset in many people with focal epilepsies often is a so-called aura (ie, sensory, gustatory, visual, olfactory, auditory or abdominal, or more complex experiential sensation[s]) experienced by the patient.²⁰ Auras in some patients occur in combinations. An aura is not necessarily present, however, and other clinical features (described later) may also present as the first seizure symptom depending on the relationship of seizure onset and symptomatogenic cortical areas.

Different clinical phenomena depend on the location and extent of the ictal onset zone and its relationship to symptomatogenic cortical areas (Fig. 1).²¹ For example, somatosensory auras (such as numbness, tingling, and painful or burning-like sensations) are usually generated from contralateral parietal areas.²² Visual auras, such as seeing simple and fixed objects, often are related to activation of occipital area (area 17). Complex visual phenomena are more likely to be generated from the right temporo-parieto-occipital junction, and when prominent movement of the visual phenomena is perceived, occipital areas 18 and 19 are frequently involved.^23,²⁴ Auditory auras can arise from the lateral temporal region unilaterally or bilaterally.²⁵ Olfactory and gustatory auras (ie, smelling of complements that are not present and abnormal tasting) are mostly related to spread into the temporal regions.²⁶

Fig. 1 Example of cortical zones in a selected epilepsy patient. The epileptogenic zone is the area of cortex indispensable for the generation of seizures. Within the epileptogenic zone, there is a smaller area, the ictal onset zone, where seizures are generated. The irritative zone is the area producing interictal epileptiform discharges. The symptomatogenic zone is the eloquent region (overlapping with the epileptogenic zone) responsible for the production of the clinical symptoms when activated during a seizure. The functional deficit zone is the area that clinically functions abnormally during periods in between seizures, as illustrated by functional imaging studies. Eloquent cortex is important for generating particular functions, including motor, sensory, language, and memory (ie, motor cortex, somatosensory cortex, visual cortex, and language areas).

(Adapted from Datta A, Loddenkemper T. The epileptogenic zone. In: Wyllie E, Cascino GD, Gidal BE, et al, editors. Wyllie’s treatment of epilepsy. Principles and practice. 5th edition. Philadelphia: Lippincott Williams & Wilkins; 2010; with permission.)

The most frequently reported auras are sensations of abdominal discomfort or a rising abdominal sensation located in the epigastric area and are, therefore, named epigastric aura.²⁷ Some patients report their seizures begin with an unspecific, unexplainable feeling, often localized to the head (cephalic aura).²⁸ Cephalic auras have been reported when seizure activity spreads into the temporal regions, the parietooccipital areas, and the frontal regions.²⁹ Autonomic auras that suggest activation of the autonomic system (palpitations, sweating, cold shivers or cold sweats, and piloerection) are most often secondary to symptomatogenic areas in the temporal or insular region.³⁰ Experiential auras, such as déjà vu (an intense feeling of visual or situational familiarity) or jamais vu (a feeling of visual or situational strangeness), are usually associated with temporal lobe seizures.^21,^31,³² Selected auras and their localizing value are listed in Table 1.

Table 1 Common auras and related localization

Aura	Descriptive Seizure Terminology	Brain Localization or Lateralization
Unpleasant or abnormal smell	Olfactory aura	Amygdala in mesial temporal lobe, left or right
Abnormal taste	Gustatory aura	Insula or secondary sensory cortex, left or right
Funny feeling in stomach, which often rises to the chest and neck	Epigastric aura	Insula or superior bank of sylvian fissure, common in mesial temporal lobe epilepsy, left or right
Déjà vu, fear, jamais vu, depersonalization, macropsia, micropsia, autoscopy	Psychic aura	Fear = amygdala Déjà vu or jamais vu = basal temporal lobe Multisensory hallucinations = temporal lobe
Buzzing sound, tone, or other noises	Auditory aura	Primary auditory cortex (Heschl gyrus), left or right
Flashing lights in left visual field	Visual aura	Right primary visual cortex (area 17)
Formed visual hallucinations in left visual field		Right association visual cortex
Left hand pain, tingling, or burning sensation	Somatosensory aura	Right primary somatosensory cortex
Sensation in both shoulders		Supplementary somatosensory cortex, left or right
Sensation in both hands		Superior bank of sylvian fissure of secondary sensory area, left or right

Seizure presentation and evolution

Seizure presentation and evolution include symptoms and behaviors that a patient displays during the events. For practical purposes of gathering and analyzing reported information, information is presented in the following major categories: (1) motor features, (2) automatisms, (3) language features, (4) autonomic features, and (5) impairment of consciousness.

Symptoms that manifest later in the seizure usually represent spread of the ictal activity to neighboring cortical regions.

Motor features include dystonic posturing; clonic movements; tonic movements; head version; epileptic spasms; eye movements, such as nystagmus or sustained conjugate eye deviation; and other complex motor movements. The types, body site, and lateralization of these motor features can help with localization and lateralization of seizures.¹⁵ For example, unilateral dystonic posturing, unilateral epileptic spasms, unilateral clonic seizures, unilateral tonic seizures, ictal nystagmus, version, or asymmetric tonic posturing (so-called figure 4) are generally indicative of seizure activity from the contralateral side of the brain (compared with the extended arm during the figure 4 prior to secondary generalization).³³^–³⁷

The temporal presentation of the features during a seizure plays a role, however. Late ipsiversion and the last clonic jerk during seizures are frequently related to seizure onset in the ipsilateral brain hemisphere.^36,³⁸ In a patient noted to have right clonic movements followed by right head version, then a generalized tonic clonic seizure, and subsequently several left arm clonic jerks toward the end of a seizure, the seizure may have started in the left hemisphere. Subsequent spread of the seizure into the other hemisphere may explain the late appearance of unilateral motor features ipsilateral to the seizure onset zone.

Automatisms are purposeless movements that may resemble simple repetitive movements or may be a complex sequence of natural-looking movements, such as picking or nestling hand movements or lip smacking, chewing, or tongue-licking movements.^36,³⁹

During a seizure, patients may also vocalize (ictal vocalization), verbalize (ictal speech), or have impaired language (ictal aphasia). Ictal speech has been localized to the nondominant temporal region.^40,⁴¹ Ictal aphasia usually arises from the dominant lateral temporal but sometimes from dominant frontal areas.^42,⁴³ Ictal vocalization is more often secondary to activity in the dominant hemisphere, involving more frequently the frontal than temporal lobes.^44,⁴⁵

Ictal emesis, ictal urinary urge, urge to defecate, and orgasmic auras have been related to seizures in the right/nondominant temporal lobe.^46,⁴⁷ Ictal sensation of cold has been reported with left temporal (or dominant temporal) lobe symptomatogenic zones. Unilateral piloerection (goose bumps) is generally related to seizures emanating from the ipsilateral hemisphere.⁴⁸ Impairment of consciousness can be seen ictally and postictally. Although the exact mechanisms for control of consciousness are not clear, emerging data show that processing of conscious information depends on the involvement of certain cortical and subcortical networks.⁴⁹ Recent data have correlated ictal alteration of consciousness with bilateral and/or left temporal lobe seizure activity.⁵⁰

Postictal symptoms

Immediately after the end of a seizure, patients may present with a variety of symptoms that may at times only become obvious during an examination of the patient. These may provide additional important information, because they may indicate the localization of the seizure focus. Todd paresis (or postictal paresis/paralysis) is focal weakness in a part of the body after a seizure.⁵¹ Postictal weakness secondary to a seizure focus is typically contralateral to the localization of the weakness⁵¹ and may affect the arm, leg, and/or face. It usually subsides completely within 24 to 48 hours after the seizure.⁵¹ Similarly, hemianopia (partial vision loss) can also present after a seizure, self-resolves, and is indicative of a contralateral seizure focus.⁵² Postictal aphasia and dysphasia are usually suggestive of a seizure arising from the dominant hemisphere.⁵³ Nose wiping can be observed after a seizure, and it has been seen more frequently ipsilateral to the side of seizure onset.^54,⁵⁵ Selected questions for history taking in epilepsy patients, including duration and recurrence patterns, are listed in Box 2.