Classification of epileptic seizures and seizure imitators. How not to get lost in diagnosis?

Monika Stančiukaitė
Faculty of Medicine, Vilnius University

Introduction

About 10% of people experience an unprovoked seizure at least once in their lifetime, but a single episode does not necessarily indicate epilepsy. Epilepsy is diagnosed in a patient who has experienced a seizure and whose brain, for certain reasons, has a pathological and long-term predisposition to recurrent seizures. Epilepsy is associated with stigma as well as psychological, social, cognitive, and economic consequences.

In recent decades, attitudes toward patients with epilepsy have changed, but fear of this condition remains common among both medical professionals and the general public. A lack of knowledge among family physicians regarding the classification, investigation, and management of seizures in patients with epilepsy is often observed. To improve the quality of life of people with epilepsy, it is necessary to provide more information about this condition. This article provides information on the classification of epileptic seizures and conditions that can mimic epileptic seizures. This should help improve the understanding and diagnosis of this condition.

Definition

In 2005, a theoretical definition of epilepsy described it as a brain disorder characterized by a long-term predisposition to seizures. A long-term predisposition to seizures is identified after the occurrence of 2 epileptic seizures separated by more than 24 hours (1). An epileptic seizure is a brief episode of symptoms or signs resulting from abnormal excessive or synchronous neuronal activity in the brain.

The International League Against Epilepsy (ILAE) confirmed that epilepsy should be considered a brain disorder that meets at least one of the following conditions:

1. At least 2 unprovoked (or reflex) seizures occurring more than 24 hours apart.
2. One unprovoked (or reflex) seizure, with a probability of subsequent seizures over the next 10 years equivalent to that after 2 unprovoked seizures (at least 60%).
3. Diagnosis of an epilepsy syndrome (2).

The risk of another seizure after a single unprovoked seizure is 40–52% (3). Following 2 unprovoked seizures, the risk of recurrence within the next 4 years is 73% (4).

Reflex seizures, for example in response to photic stimulation, are provoked seizures that should be considered epilepsy. Although these seizures are provoked, the tendency to respond repeatedly to a stimulus with a seizure meets the theoretical definition of epilepsy. Examples of provoked seizures that should not be considered epilepsy include seizures following head injury, febrile seizures, and seizures associated with alcohol withdrawal (6).

The purpose of the second point in the definition is to include situations in which some physicians and epilepsy experts consider a patient to have epilepsy after only one unprovoked seizure because the risk of seizure recurrence is very high. A single unprovoked seizure may occur in a patient who has experienced a brain injury, such as a stroke, central nervous system (CNS) infection, or trauma. In patients who have experienced such brain injuries, the risk of a second unprovoked seizure is similar to the risk of recurrent seizures following 2 unprovoked seizures (5). Examples include patients who experience a seizure at least 1 month after a stroke (5), or children who have experienced one seizure but also have clear structural or other causes and show epileptiform activity on an electroencephalogram (EEG) (7).

Seizures occurring within 24 hours of each other carry the same risk of subsequent seizures as a single seizure. Therefore, unprovoked seizures occurring within 24 hours of each other can be considered a single unprovoked seizure when assessing the risk of recurrence (8). The longer the time that has elapsed since the last seizure, the lower the risk of recurrence (9).

Epilepsy is considered resolved in individuals who have had an age-dependent epilepsy syndrome and are now older than the applicable age, as well as in those who have remained seizure-free for at least 10 years and have not taken epilepsy medication for at least 5 of those years. If epilepsy is considered resolved, this means that the person is not currently considered to have epilepsy, but there is no guarantee that it will never recur (2).

Classification

Descriptions of different types of seizures have appeared in the literature since the time of Hippocrates. Gastaut proposed a classification as early as 1964 (10, 11). There are several basic principles according to which seizures are classified. Some seizures are specific to particular age groups and depend on brain maturation.

Previous classifications were based on anatomical principles. Seizures were classified as temporal, frontal, occipital, parietal, interhemispheric, and brainstem seizures. Modern research has changed the understanding of the pathophysiological mechanisms of seizures and has shown that epilepsy is a disorder of neuronal networks rather than merely a manifestation of local anatomical abnormalities in the brain (12).

In 2017, the ILAE developed a new operational classification of epileptic seizures. In the new classification, seizures are divided into focal, generalized, and unknown-onset seizures, with each category further subdivided into motor and non-motor seizures and according to the presence or absence of impaired awareness (Table 1).

During focal seizures, preserved awareness means that the person remains aware of themselves and their surroundings, even when unable to move. Focal seizures without impaired awareness correspond to the previous term simple partial seizure, while focal seizures with impaired awareness correspond to the earlier term complex partial seizure. Impaired awareness at any point during the seizure classifies it as a focal seizure with impaired awareness.

Focal seizures with or without impaired awareness can be further classified according to either motor or non-motor symptoms reflecting the first noticeable manifestation of the seizure. In atonic seizures and epileptic spasms, awareness is usually not specified.

Cognitive seizures involve impairment of language or other cognitive domains, or positive features such as déjà vu, hallucinations, illusions, or perceptual distortions. Emotional seizures involve anxiety, fear, joy, other emotions, or affect without subjective feelings. Absence seizures are considered atypical when they have a slow onset or termination or prominent changes in muscle tone, supported by atypical, slow generalized spike-and-wave discharges on EEG. A seizure may remain unclassified because of insufficient information or an inability to assign it to another category.

After the seizure type has been identified, the next step is to determine the type of epilepsy (Figure 1). The new epilepsy classification was introduced in 2017. The third level of epilepsy classification is the identification of an epilepsy syndrome when a specific syndrome can be established. The new classification also incorporates etiology, which is often crucial and significant when selecting treatment.

Etiology

From the moment a patient presents with a first seizure, the physician must consider its possible etiology. First, a neuroimaging examination should be performed, ideally magnetic resonance imaging (MRI). This allows the clinician to determine whether epilepsy has a structural etiology.

Structural Etiology

Structural brain abnormalities increase the risk of seizures. These may include acquired structural abnormalities, such as those resulting from stroke, trauma, or infection, or congenital structural abnormalities, such as malformations of cortical development. Some forms of epilepsy are associated with specific brain abnormalities; for example, temporal lobe seizures are associated with hippocampal sclerosis.

In cases of certain structural abnormalities and a poor response to antiepileptic drugs (AEDs), surgical treatment of the structural abnormality should be considered. In some cases, the cause of seizures may involve both structural and genetic pathology, as in tuberous sclerosis.

Genetic Etiology

Genetic epilepsy results directly from a known or suspected genetic mutation. Molecular genetics helps identify mutations in numerous genes associated with epilepsy. Most mutations occur de novo, while others are inherited.

Infectious Etiology

Infectious epilepsy is the most common worldwide. Seizures of infectious etiology result from a known infection, such as meningitis or encephalitis. Common infections in certain regions include neurocysticercosis, tuberculosis, HIV, malaria, subacute sclerosing panencephalitis, cerebral toxoplasmosis, and congenital infections such as Zika virus and cytomegalovirus.

Infectious epilepsy may develop not only during an acute illness but also some time after recovery, for example following viral encephalitis.

Metabolic Etiology

Seizures in metabolic epilepsy result from a known or suspected metabolic disorder. Metabolic causes may include porphyria, aminoacidopathies, pyridoxine-dependent seizures, glucose transporter deficiency, and other disorders. In many cases, a genetic defect underlies the metabolic disorder.

Identifying a specific metabolic disorder that causes epilepsy is important for selecting specific treatment and because of its potential negative impact on intellectual function.

Immune Etiology

Immune epilepsy results from an immune system disorder that manifests with seizures. The immune etiology of epilepsy was identified relatively recently. Immune etiology can be understood as CNS inflammation caused by an autoimmune process, such as autoimmune encephalitis.

Unknown Etiology

There is still a proportion of patients in whom the cause of epilepsy remains unclear.

Epilepsy Mimics

Several conditions can cause recurrent paroxysmal events that may mimic epilepsy and be mistakenly diagnosed as epileptic seizures.

Syncope and Breath-Holding Spells

Syncope is a transient loss of consciousness caused by a sudden decrease in cerebral blood flow and oxygen supply. Syncope can occur at any age, while breath-holding spells are more common in infants and young children. A detailed history helps identify the cause and differentiate syncope from epilepsy.

Early symptoms of syncope include blurred vision, loss of vision, ringing in the ears, and dizziness, and may also include pathological and autonomic symptoms such as flushing, sweating, warmth, nausea, and abdominal discomfort. Stiffening or myoclonus occurs in approximately 50% of cases of syncope. These movements are shorter than those occurring during epileptic seizures and are more often arrhythmic. Confusion after an episode is usually very brief, while confusion lasting longer than 10 minutes indicates an epileptic seizure.

Reflex anoxic seizures or reflex asystolic syncope occur from early infancy and usually resolve by preschool age or develop into vasovagal syncope. In such cases, an unpleasant and usually sudden stimulus, such as a blow to the head, a cut, or a scratch, causes vasodilation and slows the heart rate (18). An anoxic seizure may occur with or without tonic and clonic movements. Neither syncope nor an anoxic seizure occurs because of an epileptic discharge in the brain.

Chiari malformation may be a cause of neurogenic syncope. In this developmental disorder, severe coughing or straining may lead to temporary loss of consciousness when increased intracranial pressure causes brain herniation that compresses arteries and cranial nerves IX and X.

It is important to recognize long QT syndrome and cardiogenic syncope because these conditions are life-threatening. In long QT syndrome, ventricular tachyarrhythmia may occur spontaneously or be triggered by fear, physical exertion, or submersion in water. Syncope during sleep, a family history of syncope, or a family history of early death should raise suspicion of cardiogenic syncope (19).

Behavioral, Psychological, and Psychiatric Disorders

Daydreaming commonly occurs in childhood and may be incorrectly diagnosed as absence seizures. Daydreaming can be interrupted by calling the child or clapping loudly, whereas during an absence seizure the patient does not respond when called.

Psychogenic seizures resemble epileptic seizures but have no electroencephalographic correlates or clinical evidence of epilepsy. The etiology of non-epileptic seizures is heterogeneous because different individuals have different predisposing and triggering factors. A seizure-like event may involve movements and impaired perception, mimicking focal motor seizures.

Features that distinguish these attacks from epileptic seizures include a predominance of proximal movements, varying speed and direction of twitching, horizontal head movements, crying during or after the event, eye closure, and resistance to passive eye opening (20). EEG monitoring and psychiatric evaluation are usually required to establish the diagnosis (21).

Self-stimulation, stereotypies, hysterical seizures, panic attacks, and hallucinations associated with mental disorders may mimic epilepsy (19). A detailed seizure history and EEG are important for establishing an accurate diagnosis.

Sleep-Related Disorders

Benign myoclonus of infancy at sleep onset is a normal condition that occurs at the beginning of sleep and is sometimes mistakenly confused with myoclonic epilepsy.

Parasomnias are common and may be considered a normal part of sleep unless the associated behavior causes concern. Parasomnias can vary from sitting up in bed and talking to walking, talking loudly, shouting, and other behaviors. These events may be misdiagnosed as temporal lobe seizures. Family history often reveals a genetic predisposition (22).

Periodic leg movements during sleep may be associated with restless legs syndrome. They are characterized by repetitive flexion of the toes, knees, and hips, sometimes involving the upper limbs. Strong leg jerks may be misdiagnosed as myoclonic epilepsy.

Narcolepsy-cataplexy is a lifelong neurological disorder affecting the boundaries of sleep-state control, in which the distinction between sleep states, particularly REM sleep, and wakefulness becomes blurred. Cataplexy involves sudden physiological REM atonia associated with strong emotions, particularly laughter. It may cause head nodding, facial muscle weakness, knee buckling, and collapse. The person remains conscious, although the eyes may be closed (19).

Paroxysmal Movement Disorders

These are involuntary, sudden, rapid, repetitive, arrhythmic, uncomplicated, simple or complex movements or vocalizations. Typically, the movements involve one muscle or muscle group, including the eye muscles, and may therefore be mistaken for myoclonic seizures.

Complex motor tics involve a group of simple actions or a coordinated sequence of movements and may be misdiagnosed as focal seizures without impaired awareness (23). The urge to perform a tic and the ability to suppress it for a certain period are important features in differentiating the condition.

Disorders Related to Migraines

Benign paroxysmal torticollis is considered a variant of migraine in infancy and early childhood. The infant may appear pale, vomit, and seem distressed. Older children may experience ataxia.

Benign paroxysmal vertigo is considered a variant of migraine in childhood. It involves a subjective experience described by the child. Children may become anxious, stop moving, hold onto an adult, or lie down. Episodes last for a few minutes and occasionally for several hours. Vomiting and nystagmus may also occur. These episodes may mimic focal seizures.

Episodes of cyclic vomiting may be confused with focal epileptic seizures, but awareness remains intact during cyclic vomiting, and the episodes last longer (19).

Various Events

Benign infantile myoclonus and tremor seizures are benign and resolve spontaneously. These seizures begin in infants from 4 months of age and may persist until 6–7 years of age. They can occur very frequently and last for several seconds. Certain activities, such as feeding, head movements, or specific tasks, may trigger the seizures. These events do not cause distress to the child, and children return to their previous activities afterward. They may be misdiagnosed as myoclonic jerks or epileptic spasms.

Sandifer's syndrome occurs in young children with gastroesophageal reflux, with or without vomiting. Paroxysms are often observed during or after feeding. They typically involve twisting of the back and turning or tilting of the head. Arching of the back during or after feeding is the main feature that distinguishes this disorder from epileptic seizures.

Non-epileptic head nodding develops in infants and may mimic epileptic spasms or atonic seizures. Infants usually experience more than 100 head nods per day, which may be pronounced and occur in series, causing head banging. Neck flexion and head elevation occur at the same speed, unlike during an epileptic seizure. When these paroxysms begin, the infant's development is not affected (19).

Summary

Epilepsy is a brain disorder that meets at least one of the following conditions:

• At least 2 unprovoked (or reflex) seizures occurring more than 24 hours apart.
• 1 unprovoked (or reflex) seizure, with a probability of recurrent seizures over the next 10 years equivalent to that following 2 unprovoked seizures (at least 60%).
• Diagnosis of an epilepsy syndrome.

A properly collected medical history allows the seizure to be accurately described and an epileptic seizure to be differentiated from other disorders. Timely and accurate diagnosis and determination of etiology can help patients overcome fears, stigma, and psychosocial problems associated with the diagnosis. In infants and young children, this may also help improve development and halt developmental regression.

It is increasingly recognized that many cases of epilepsy are associated with comorbidities, including learning, psychological, and behavioral problems. The severity of comorbid problems varies from subtle learning difficulties to intellectual or psychological disorders, including autism spectrum disorders and depression, as well as psychosocial problems. Individuals with severe epilepsy may also have motor disorders, including cerebral palsy, impaired gait and movement, and scoliosis, as well as sleep and digestive system disorders. Once the diagnosis has been established, it is important to assess comorbid conditions so that the necessary assistance can be provided as early as possible.

Table 1. ILAE 2017 Seizure Classification

Journal "Internistas" No. 3, 2020

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