Nonepileptic paroxysmal disorders in adolescents and adults

INTRODUCTION AND DEFINITION — 

Nonepileptic paroxysmal events are defined as sudden, episodic, involuntary changes in behavior, sensation, or consciousness that resemble epileptic seizures but are not accompanied by abnormal ictal discharges in the brain [1]. The term "epileptic seizure" refers to a transient occurrence of signs and/or symptoms due to abnormally excessive neuronal activity of the brain. Epilepsy is a condition characterized by recurrent seizures.

While it is estimated that 0.5 to 1 percent of the population has epilepsy, nearly 25 percent of patients seen in epilepsy clinic and monitoring units do not have epilepsy [2-5]. It is important for clinicians to recognize these transient nonepileptic events that may resemble seizures to avoid unnecessary treatment with antiseizure drugs and to institute the correct treatment when appropriate.

The symptoms of epileptic seizures are diverse. As a result, disorders that might be considered in the differential diagnosis will vary depending on the patient's specific clinical presentation. Clearly, not all of these disorders are considered in any one patient.

Nonepileptic paroxysmal events that can be mistaken for epilepsy also differ by age group (table 1). This topic will review those diagnoses in adolescents and adults. These diagnoses can be classified into several broad categories:

●Syncope

●Psychologic disorders

●Sleep disorders

●Paroxysmal movement disorders

●Migraine

●Other transient neurologic events (eg, transient ischemic attack)

●Hallucinations

Disorders more prevalent in childhood can occasionally present or persist into adulthood as well. Nonepileptic paroxysmal events that are more prevalent in other age groups are reviewed separately:

●(See "Nonepileptic paroxysmal disorders in neonates and infants".)

●(See "Nonepileptic paroxysmal disorders in children".)

●(See "Seizures and epilepsy in older adults: Etiology, clinical presentation, and diagnosis", section on 'Differential diagnosis'.)

Functional seizures, also known as psychogenic nonepileptic seizures (PNES), are discussed in detail elsewhere. (See "Functional seizures: Etiology, clinical features, and diagnosis".)

SYNCOPE — 

Syncope is an abrupt loss of consciousness due to an interruption of energy sources to the brain, usually because of a sudden reduction of cerebral perfusion (see "Syncope in adults: Clinical manifestations and initial diagnostic evaluation"). It is common to confuse seizure with syncope as the cause of an isolated or episodic loss of consciousness [6-9], especially but not exclusively when the episode is not witnessed.

Clinical features — A careful clinical history is important in distinguishing syncope from epilepsy [10]. Key features are not always volunteered and must be specifically solicited.

●Clinical setting – Epileptic seizures and syncope can occur in any setting and are often unprovoked [11,12]. Vasovagal syncope tends to occur in the setting of a strong emotional or painful stimulus but may also occur with more subtle stimuli, including a hot environment. Reflex syncopes occur with specific stimuli (eg, micturition, cough). Events in the setting of exertion suggest syncope related to structural cardiac disease. Except when caused by a cardiac arrhythmia, it is unusual for syncope to occur when the patient is supine.

●Warning symptoms (aura, prodrome) – In vasovagal syncope, a prodrome of presyncope is the rule. These patients may note lightheadedness, warmth, sweating, nausea, and a gradual fading or tunneling of binocular vision. They may reach out to steady themselves. By contrast, symptoms of olfactory hallucinations or déjà vu suggest a seizure aura. However, not all epileptic seizures include a seizure aura. Cardiogenic syncope typically occurs without warning.

●Associated symptoms – Pallor and diaphoresis strongly suggest syncope [8]. However, it is unusual for syncope to be associated with lateral tongue biting, head or eye turning to one side, or foaming at the mouth; these suggest epileptic seizure [8,10,13-15]. Urinary incontinence can occur in both seizures and syncope.

●Motor activity (convulsive syncope) – While motor activity during an episode of unconsciousness often suggests a seizure diagnosis, brief motor activity, including tonic extension of the trunk and limbs or several clonic jerks, can occur in uncomplicated syncope [12,16]. The severity of convulsive symptoms in syncope varies from subtle signs that are often overlooked to more dramatic symptoms that mimic an epileptic seizure. The combination of seizure-like motor activity in the setting of syncope is sometimes referred to as convulsive syncope. Convulsive syncope is usually brief (<20 seconds).

Relatively few bystanders witnessing syncopal attacks report convulsive symptoms, but clinicians systematically observing attacks (eg, during tilt table testing, invasive cardiac electrophysiologic testing, blood drawing) describe convulsive symptoms in up to half of patients [7,13,17-19]. While these convulsions are common in syncope, a true epileptic seizure ("anoxic seizure") is rare, except in susceptible people or those with prolonged and more severe cerebral ischemia [6,17,20].

Electroencephalography (EEG) recordings during syncopal events usually demonstrate generalized slowing followed by high-voltage frontal delta activity [20,21]. Flattening of the EEG can follow if cerebral hypoperfusion persists. It is at this stage that nonepileptic, seizure-like movements are most often described. It has been suggested that these movements may represent a brainstem-release phenomenon.

●Recovery of consciousness – Patients usually wake up quickly after a syncopal event and may recognize their surroundings within a minute or so. Prolonged confusion or lethargy lasting several minutes or longer favors seizure [8].

Causes of syncope

●Vasovagal syncope – Vasovagal syncope is the most prevalent cause of syncope [21]. This often occurs in response to clinical setting (eg, painful procedures, blood drawing, warm setting). In susceptible individuals, autonomic activation leads to a hyperactive parasympathetic cardioinhibitory response and/or a diminished sympathetic response leading to vasodepression and syncope. (See "Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation", section on 'Vasovagal syncope'.)

●Situational syncope – This type refers to events that are believed to reflect vagal hypersensitivity to specific stimuli (eg, micturition and cough syncope, carotid sinus hypersensitivity) [20]. These diagnoses are suggested by the specific provocation under which they occur. (See "Syncope in adults: Epidemiology, pathogenesis, and etiologies".)

●Cardiogenic syncope – Cardiogenic syncope related to either tachy- or bradyarrhythmias is less common but carries a more ominous prognosis. These events are usually unprovoked. Structural heart disease (eg, aortic stenosis) can also lead to syncope by obstructing blood flow. (See "Syncope in adults: Epidemiology, pathogenesis, and etiologies", section on 'Cardiac arrhythmias'.)

In rare cases, epileptic seizures can induce a cardiac arrhythmia. The most commonly described of these phenomena is an ictal bradycardia in the setting of a temporal lobe seizure [22,23]. (See "Sudden unexpected death in epilepsy".)

●Orthostatic hypotension – This is more common in older adults than in younger adults, but should be excluded when convulsive syncope is considered in the differential diagnosis [24]. Orthostatic hypotension is defined as a systolic blood pressure decrease of at least 20 mmHg or a diastolic blood pressure decrease of at least 10 mmHg after three minutes of standing. Syncope occurs in the setting of either prolonged standing or a sudden assumption of upright posture. In a first attack, acute blood loss should be excluded. Autonomic neuropathy from diabetes and antihypertensive drugs are some of the more common causes of recurrent episodes. (See "Mechanisms, causes, and evaluation of orthostatic hypotension".)

●Hyperventilation – Hyperventilation with hypocapnia can lead to presyncope and rarely to syncope [25-27]. In adolescents and adults, this may be seen in the setting of a panic attack. The presumed mechanism involves respiratory alkalosis causing widespread vasoconstriction, which in turn decreases cerebral blood flow. Patients often have prodromal complaints of dyspnea, circumoral or acral paresthesias, and visual phosphenes. Tetany, muscle cramps, carpopedal spasm, and chest pain can also occur. A three-minute trial of hyperventilation may induce similar symptoms and aid in diagnosis [11]. (See 'Panic attacks' below.)

●Evaluation – The clinical features described above are helpful in distinguishing syncope from seizure. However, in many cases, these features are unclear or equivocal, and testing is required. The history should focus on potential precipitants and eyewitness descriptions of the event and the recovery (postictal) period; the examination should focus on vital signs and cardiac, pulmonary, and neurologic evaluations.

Initial diagnostic testing typically involves rapid point-of-care glucose, electrocardiogram (ECG), and serum lactate (if concern for seizure). Additional testing (eg, neuroimaging, EEG) may be indicated if suspicion for seizure persists after the initial evaluation or if the cause remains unknown. A home video recording of the event can prove invaluable to judge the qualitative aspects of the spell.

Because the prevalence of syncope in the emergency department is far higher than that of seizures, the positive predictive value of EEG abnormalities is low, rendering EEG testing of questionable use in this setting. Only if the EEG captures an event will it help confirm or refute seizures.

The evaluation of suspected syncope is discussed in detail separately:

•(See "Approach to the adult patient with syncope in the emergency department".)

•(See "Syncope in adults: Clinical manifestations and initial diagnostic evaluation".)

•(See "Syncope in adults: Risk assessment and additional diagnostic evaluation".)

•(See "Emergency evaluation of syncope in children and adolescents".)

The initial evaluation of seizure is also discussed in detail separately:

•(See "Evaluation and management of the first seizure in adults", section on 'Initial evaluation'.)

•(See "Seizures and epilepsy in children: Clinical and laboratory diagnosis".)

PSYCHOLOGIC DISORDERS

Functional seizures — Functional seizures, also known as psychogenic nonepileptic seizures (PNES), are events thought to have mainly psychologic origins. They clinically mimic epileptic seizures or syncope but are not associated with abnormal neuronal activity or reduced perfusion to the brain. Functional seizures include a variety of clinical manifestations, some of which are suggestive, although not independently diagnostic, in distinguishing functional seizures from other differential diagnoses; these are listed in the table for convulsive functional seizures (table 2) and swoon functional seizures (table 3), the two most common forms. Video-EEG monitoring is usually required for diagnosis.

Functional seizures are discussed in detail separately. (See "Functional seizures: Etiology, clinical features, and diagnosis".)

Panic attacks — Panic attacks may be seen in the context of many different psychiatric or medical disorders (eg, anxiety disorders, posttraumatic stress disorder, cardiovascular disorders, pulmonary disorders). The attack is characterized by an abrupt surge of intense fear or discomfort; symptoms typically reach a peak within minutes and resolve within an hour. During an attack, manifestations may include palpitations, dyspnea, chest pain, presyncope, and a sense of impending doom. Patients often manifest tachycardia, diaphoresis, and tremulousness during the attack. (See "Panic disorder in adults: Epidemiology, clinical manifestations, and diagnosis", section on 'Panic attacks'.)

When not clearly precipitated by stressful circumstances or when associated with feelings of depersonalization or derealization, panic attacks may be mistaken for seizures. Similarly, seizures can be mistaken for panic attacks because anxiety is a common comorbid condition in individuals with epilepsy, and fear can be an ictal symptom, particularly in temporal lobe epilepsy [28,29]. (See "Focal epilepsy: Causes and clinical features", section on 'Mesial temporal lobe epilepsy'.)

Clinical features that help distinguish epileptic seizures from panic attacks include their short duration (less than two to three minutes), stereotyped nature, abrupt onset, motor automatisms, altered awareness or consciousness, sensory or psychic phenomena (eg, déjà vu, jamais vu), and postictal lethargy, all of which are atypical for panic attacks. (See "Panic disorder in adults: Treatment overview".)

Episodic dyscontrol — Individuals with episodic dyscontrol, also called intermittent explosive disorder (IED), display episodes of rage and violence. This disorder usually presents in teenagers and young adults, although it can occur in younger children as well. (See "Intermittent explosive disorder in adults: Epidemiology and pathogenesis", section on 'Sociodemographic correlates'.)

Behavior exhibited during these episodes can appear as though the individual is "out of control." Other features of the episodes that resemble epileptic seizures include their abrupt onset, often without apparent precipitant, and their short duration, often followed by fatigue and remorse. However, the directed violence of these episodes is rarely a feature of epileptic seizures. (See "Intermittent explosive disorder in adults: Clinical features, assessment, and diagnosis".)

SLEEP DISORDERS

Specific disorders

Narcolepsy — Narcolepsy is a rare sleep disorder associated with rapid eye movement (REM) sleep invading normal wakefulness. The tetrad of clinical features includes (see "Clinical features and diagnosis of narcolepsy in adults", section on 'Core symptoms'):

●Excessive daytime sleep – Irresistible sleepiness can culminate in a "sleep attack," in which sleep onset can occur while talking, driving, or walking.

●Cataplexy – This sudden loss of muscle tone with preserved consciousness can be mistaken for an atonic seizure. Cataplexy can result in falls and brief paralysis but more often is limited to buckling of the knees and slurring of speech. The attacks are classically precipitated by strong emotion, most commonly laughter but also anger, fear, surprise, or excitement; this feature helps distinguish these attacks from an epileptic seizure.

●Sleep paralysis – Sleep paralysis is an inability to move or speak that typically occurs upon awakening or falling asleep and lasts less than 10 minutes. Sometimes, the episodes resolve when someone touches the patient. These can be very frightening to the patient who maintains consciousness throughout the event.

●Hypnagogic and hypnopompic hallucinations – These are usually visual and less often somatosensory, auditory, vestibular, or olfactory hallucinations that occur while falling asleep (hypnagogic) or on awakening (hypnopompic). The content can be simple (a brief image of a face) or complex (an entire scene occurring in the room). The patient is fully aware during the episode. (See 'Hallucinations' below.)

Only a minority of patients with narcolepsy experience all these symptoms. When daytime sleep attacks, cataplexy, hypnagogic hallucinations, and sleep paralysis occur as isolated features, they may be mistaken for epilepsy and vice versa [30-32]. Polysomnography and a multiple sleep latency test (MSLT) aid in the diagnosis of narcolepsy, as discussed separately. (See "Clinical features and diagnosis of narcolepsy in adults", section on 'Diagnostic evaluation'.)

Hypnic jerks — Most people have experienced a sudden jerking movement upon falling asleep, often accompanied by a subjective sensation of falling. This phenomenon, also known as benign hypnic myoclonus or sleep starts, is usually easily recognized. Rarely, hypnic jerks can become unusually violent, very frequent, or repetitive, and they can be confused for myoclonic seizures or even tonic-clonic seizures. Hypnic jerks are restricted to sleep, always or virtually always occur in the transition between sleep and wakefulness, and are not associated with other phenomena. (See "Approach to abnormal movements and behaviors during sleep", section on 'Simple or single movements'.)

Nocturnal paroxysmal dystonia — Nocturnal paroxysmal dystonia or paroxysmal hypnogenic dyskinesia is a name originally given to repeated dystonic or dyskinetic episodes that occurred during or immediately after arousal from non-REM (NREM) sleep or, more rarely, during wakefulness [33-35]. These episodes typically last less than one minute, sometimes up to one hour, and often recur several times per night. The movements are often violent and may result in injury to the patient or bed partner. Patients do not recall the events.

This condition has been reported in children and adults, can be isolated or familial, and is persistent [34,35]. These episodes are often not associated with epileptiform EEG activity or other abnormal EEG findings. However, findings of epileptiform activity on zygomatic and sphenoidal leads and response to antiseizure drugs in some patients suggest that this disorder is of epileptic origin, a manifestation of sleep-related hypermotor epilepsy (previously called nocturnal frontal lobe epilepsy) [35,36]. Nevertheless, the evidence supporting epilepsy as the cause is considered weak by some experts [37]. (See "Focal epilepsy: Causes and clinical features", section on 'Frontal lobe epilepsy' and "Sleep-related epilepsy syndromes".)

Restless legs syndrome and periodic limb movements of sleep — Restless legs syndrome (RLS) refers to symptoms of discomfort in the legs that occur at rest and are relieved by movement. The hallmark symptom of RLS is a highly unpleasant or uncomfortable urge to move the legs (and occasionally the arms). The symptom emerges during periods of inactivity, is most prominent in the evening, and is transiently relieved by movement. Patients may resort to hitting their legs to relieve the discomfort.

RLS is frequently associated with involuntary, jerking movements of the legs during sleep, known as periodic limb movements of sleep (PLMS), defined as periodic episodes of repetitive and highly stereotyped limb movements that occur during sleep. The intensity and anatomic distribution of the movements vary from slight extension of the great toe to a prominent triple flexion of the entire leg and occur at periodic intervals of 20 to 40 seconds, which is unlike an epileptic seizure. PLMS does not include vocalizations or facial movements. (See "Clinical features and diagnosis of restless legs syndrome and periodic limb movement disorder in adults".)

PLMS usually occur in stages N1 and N2 of NREM sleep, early in the night, and in clusters lasting minutes to hours. Patients may be unaware of the movements, which are often more bothersome to the bed partner. Polysomnography and/or EEG monitoring may aid in the diagnosis. (See "Clinical features and diagnosis of restless legs syndrome and periodic limb movement disorder in adults", section on 'Periodic limb movements of sleep'.)

Sleep-related rhythmic movement disorder — Rhythmic movements such as nocturnal head banging, body rocking, and head rolling typically occur in young children as they try to fall asleep [38]. Episodes usually resolve by five years of age but can persist into adult life [39,40]. (See "Sleep-related movement disorders in childhood", section on 'Rhythmic movement disorder'.)

Sleepwalking and other disorders of arousal — Brief nocturnal arousals occurring during NREM sleep can manifest as confusional arousals, sleepwalking, and night terrors. These conditions are most common in children between 4 and 12 years of age and usually resolve during late adolescence. However, sometimes symptoms persist into adulthood, and up to 15 percent of cases begin in adolescence or adulthood. The emergence of sleepwalking or other disorders of arousal in adults should prompt consideration of common provocative factors, such as sleep deprivation, medications or substances, or a comorbid sleep disorder associated with frequent arousals, such as obstructive sleep apnea. (See "Parasomnias of childhood, including sleepwalking" and "Disorders of arousal from non-rapid eye movement sleep in adults".)

REM sleep behavior disorder — REM sleep behavior disorder (RBD) is a parasomnia characterized by dream enactment that emerges after a loss of REM sleep atonia. Behaviors are brief, correlate with dream mentation, mainly occur in the second half of the night, and, when violent, can result in injury to the patient or bed partner.

RBD is most common in older adults in association with alpha-synuclein neurodegenerative disorders including Parkinson disease, multiple system atrophy, and dementia with Lewy bodies. In adolescents and younger adults, RBD is more often associated with a medication (particularly serotonergic antidepressants), narcolepsy, or pontine lesions from multiple sclerosis or other etiologies. (See "Rapid eye movement sleep behavior disorder".)

Diagnostic approach — Because of their episodic and often paroxysmal nature, parasomnias and other sleep disorders may be confused with epilepsy [32]. An exclusive nighttime occurrence of events may suggest a sleep disorder but does not exclude epilepsy, as this is a characteristic of certain epileptic disorders such as nocturnal frontal lobe epilepsy and juvenile myoclonic epilepsy (JME) [13,41]. (See "Sleep-related epilepsy syndromes", section on 'Sleep-related focal epilepsies' and "Juvenile myoclonic epilepsy".)

Specific features of the events, including duration, frequency, timing, stereotypy, and vocalizations, can help distinguish nocturnal seizures from sleep disorders (table 4A-C). The Frontal Lobe Epilepsy and Parasomnias (FLEP) Scale is a questionnaire that can help distinguish parasomnias from nocturnal frontal lobe seizures [42]. Recording episodes on video-EEG and polysomnography remains necessary when the diagnosis is unclear [34,41]. (See "Approach to abnormal movements and behaviors during sleep", section on 'Evaluation'.)

Epilepsy and sleep disorders can also co-occur (see "Sleep-related epilepsy syndromes"). As an example, disorders of arousal (eg, sleepwalking, confusional arousals) are common in patients with nocturnal frontal lobe epilepsy and their relatives. (See "Disorders of arousal from non-rapid eye movement sleep in adults", section on 'Association with sleep-related hypermotor epilepsy'.)

MOVEMENT DISORDERS — 

Hyperkinetic movement disorders or dyskinesias include chorea, dystonia, athetosis, tics, tremors, and ballism. These are described separately. (See "Hyperkinetic movement disorders in children".)

Specific disorders

Myoclonus — Myoclonus is characterized by brief, shock-like, involuntary movements caused by muscular contractions (positive myoclonus) or inhibitions (negative myoclonus or asterixis). Myoclonus is associated with numerous etiologies, pathophysiologic mechanisms, and clinical syndromes (table 5). Thus, the differential diagnosis of myoclonus is broad and includes epileptic seizures, toxic-metabolic derangements (including drug-induced), normal physiologic phenomena, and others [43]. (See "Classification and evaluation of myoclonus", section on 'Causes'.)

The evaluation of myoclonus begins with clinical observation and a detailed history; in many cases, additional testing with blood tests, EEG, electromyography (EMG), evoked potentials, and/or neuroimaging may be needed to determine the etiology (table 6). The evaluation of myoclonus is reviewed in detail separately. (See "Classification and evaluation of myoclonus", section on 'Evaluation'.)

Paroxysmal dyskinesias — These paroxysmal movement disorders are rare forms of dystonia that are characterized by episodes of spontaneous or induced dyskinesia with dystonia. They are briefly described below and are discussed separately. (See "Etiology, clinical features, and diagnostic evaluation of dystonia", section on 'Paroxysmal dyskinesia with dystonia'.)

The diagnosis of these disorders is based in large part on history; causes include genetic variants, infections, metabolic derangements, structural brain malformations, and malignancies [44]. A video-EEG recording of events is invaluable in difficult cases [32].

●Paroxysmal kinesigenic dyskinesia (PKD) – Also known as paroxysmal kinesigenic choreoathetosis, PKD consists of brief (less than one minute) attacks of choreoathetosis, dystonia, or both, which are precipitated by the initiation of normal movements; getting up from a chair and getting out of a car are frequent triggers. Movements are often unilateral but may be bilateral. Consciousness is retained. Many individuals may have a brief, nonspecific warning or aura prior to an attack. The interictal examination is normal. The disorder may be a hereditary, sporadic/idiopathic, or secondary condition (due to multiple sclerosis, stroke, traumatic brain injury). Men are affected more often than women.

●Paroxysmal nonkinesigenic dyskinesia (PNKD) – This disorder consists of attacks of spontaneous, severe dystonia that may be precipitated by alcohol, caffeine, and stress. These episodes last two minutes to several hours, and sometimes two days. Antiseizure medications can be efficacious, but their efficacy is less consistent than it is in PKD. Familial, sporadic, and secondary forms have been described.

●Paroxysmal exercise-induced dyskinesia (PED) – This disorder consists of brief episodes of dystonia that occur after several minutes of exercise, not at initiation of movement as in PKD. Typically, the part of the body that has been doing the most exercise becomes dystonic. The abnormal movement resolves gradually with cessation of the exercise. This may be a sporadic or hereditary condition. In general, antiseizure drugs are not helpful. Acetazolamide has been effective in some families.

Tics and stereotypies

●Tics – These are relatively brief, sudden, rapid, and intermittent movements (motor tics) or sounds (vocal tics). They may be repetitive and stereotypic. Tics are usually abrupt in onset and brief (clonic tics) but may be slow and sustained (dystonic tics). Tics are associated with a premonitory feeling that is relieved by performing the tics. Unlike other hyperkinetic dyskinesias and unlike epileptic seizures, tics may be temporarily suppressed. Tics also differ from epilepsy by the variability of the movement and the urge to perform tics. The myoclonic jerks of juvenile myoclonic epilepsy (JME) can be mistaken for tics, but these cannot be suppressed, have no premonitory sensation, and are quicker and more stereotyped [45,46]. (See "Juvenile myoclonic epilepsy", section on 'Seizures'.)

Tics can occur as part of Tourette syndrome but may also be an isolated phenomenon. More clinical details about the evaluation and treatment of a patient with tics is presented separately. (See "Tourette syndrome: Pathogenesis, clinical features, and diagnosis" and "Tourette syndrome: Management".)

●Stereotypies – Also called mannerisms, stereotypies are repetitive, purposeless actions such as head banging, head rolling, body rocking, and hand flapping [47]. Like tics, stereotypies may be consciously suppressed and decreased by distraction. Unlike tics, stereotypies are not preceded by a progressive urge or relief following the activities. Often, they manifest as self-stimulating behaviors in response to tension and anxiety and may comfort the patient. Stereotypies may occur alone or may be secondary to trauma, drugs (eg, chronic amphetamine abuse), or toxic-metabolic insult. These movements can also be seen in otherwise healthy individuals but are more common in those with schizophrenia, intellectual disability, and autism. (See "Hyperkinetic movement disorders in children", section on 'Stereotypies'.)

Hemifacial spasm, blepharospasm, and Meige syndrome

●Hemifacial spasm – This is characterized by involuntary synchronous spasms of one side of the face, usually beginning around the eye [48]. They are typically brief, irregular clonic movements but are occasionally tonic. Onset is most common in midlife. The disorder almost always presents unilaterally, although bilateral involvement may occur in severe cases (fewer than 5 percent overall) [49]. Brief clonic movements are first noted in the orbicularis oculi and spread over months to years to involve other facial muscles. It never involves muscles other than those innervated by the facial nerve. Patients cannot suppress the movements. Unlike other movement disorders, the spasms can continue during sleep. Complete remission is rare. (See "Classification and evaluation of myoclonus", section on 'Anatomic and physiologic classification'.)

Treatment is reviewed elsewhere. (See "Treatment of myoclonus", section on 'Hemifacial spasm'.)

●Blepharospasm – This is a focal dystonia characterized by involuntary contractions of the orbicularis oculi and other periocular muscles, resulting in the bilateral closure of the eyes. This can range from a relatively benign increase in blink frequency to sustained eyelid closure and functional blindness. Onset is gradual and usually occurs in midlife. (See "Etiology, clinical features, and diagnostic evaluation of dystonia", section on 'Blepharospasm'.)

●Meige syndrome – A craniocervical dystonia, Meige syndrome encompasses the dystonic contractions of blepharospasm in addition to spasms of the lower facial muscles, jaw, and neck [50,51]. Both blepharospasm and Meige syndrome may involve bilateral facial muscle contractions. Most cases have no known etiology. However, these symptoms can be seen because of chronic neuroleptic medication.

When unilateral, these conditions can be mistaken for epilepsia partialis continua, and vice versa [52-54]. A routine EEG is usually sufficient for diagnosis.

Stiff-person syndrome — Stiff-person syndrome (SPS) is characterized by progressive muscle stiffness and rigidity with superimposed episodic and painful muscle spasms. It is reviewed in detail separately. (See "Stiff-person syndrome".)

SPS predominantly affects the axial and proximal limb muscles. Muscle spasms are aggravated by sudden movement and by emotional, somatosensory, or acoustic stimuli. Startle-induced spasms are common and may be mistaken for stimulus-induced seizures. However, the presence of pain and the sustained spasms with muscle rigidity between spasms are not typical for epilepsy.

SPS is frequently associated with markedly elevated levels of antibodies against glutamic acid decarboxylase or amphiphysin. EMG may be helpful in the diagnosis and usually shows continuous low-frequency firing of normal motor action potentials without the ability of voluntary relaxation. EEG is normal.

Distinguishing movement disorders from seizures — Movement disorders are rarely confused with seizures if the motor activity is classic in appearance and is sustained rather than episodic. Also, impaired consciousness does not occur with movement disorders and, when present, strongly suggests seizures. However, it can be difficult to differentiate these when movement disorders present with episodic symptoms and when focal epileptic seizures are characterized by isolated dystonic posturing or have continuous symptoms (epilepsia partialis continua). Of note, because of their deep interhemispheric focus, focal seizures of the leg may not produce an epileptiform EEG recording at the scalp.

Some patients with dystonia and other movement disorders may obtain symptomatic relief from sensory tricks, such as lightly touching their faces to ameliorate cervical dystonia [55]. This phenomenon is known as geste antagoniste and may be a useful feature distinguishing dystonic movements from epilepsy.

MIGRAINE — 

Both migraine and epilepsy are characterized by episodes of neurologic dysfunction that are accompanied by headache, as well as gastrointestinal, autonomic, and psychologic features. Clinical features common to both migraine and epilepsy include:

●Headache – This is a cardinal feature of migraine but is also a common postictal event, reported in 40 to 45 percent of both pediatric and adult patients with epilepsy [56-64]. This postictal headache often has migrainous features, can last more than a few hours, and occurs after both partial and generalized seizures.

However, a third or more of patients with migraine do not have headaches with at least some of their migraine events [65]. Sometimes called migraine dissociée, the confidence in making this diagnosis is considerably higher if the patient has previously had similar episodes associated with headaches. (See "Pathophysiology, clinical manifestations, and diagnosis of migraine in adults".)

●Visual aura – This is a feature of classic migraine and occipital epilepsy. In both disorders, simple hallucinations are more common than complex ones; the images are binocular and often spread or move. Epileptic visual auras tend to include highly colored, circular, or spherical images that move rapidly, are stereotyped, and are relatively brief (a few minutes or less) [57,66,67]. By contrast, migrainous auras are more linear or geometric in appearance, tend to build and spread over several minutes, and last for several minutes to an hour. (See "Approach to the patient with visual hallucinations", section on 'Migraine aura' and "Approach to the patient with visual hallucinations", section on 'Seizures'.)

●Somatosensory symptoms – These can occur in both migraine and seizures. As with the visual aura, somatosensory aura symptoms in migraine spread slowly over several minutes to an hour, while in seizures the symptoms spread quickly and rarely last more than a few minutes. (See "Pathophysiology, clinical manifestations, and diagnosis of migraine in adults", section on 'Migraine aura'.)

●Auditory symptoms – These are a rare manifestation of migraine and epilepsy. In migraine, these may be unformed, ringing, clicking, buzzing, humming, hissing, rumbling, or growling noises [68]; some patients report hearing human voices in close temporal association with the headache phase of migraine, although not clearly in association with migraine aura [69]. In epileptic aura, auditory symptoms range from unformed to complex (eg, voices, music) but again are brief and stereotyped compared with migraine [70]. (See 'Hallucinations' below.)

Acute neurologic events due to migraine can be misdiagnosed as seizure or stroke, particularly migraine with uncommon manifestations. Motor activity and loss of consciousness during an episode are unusual for migraine and suggest epilepsy. Prolonged confusion, lethargy, or motor weakness after an attack also favor epilepsy but can occur in some forms of migraine. Examples include:

●Migraine with brainstem aura – This is a rare form of migraine characterized by aura symptoms of brainstem dysfunction without motor weakness. The auras consist of two or more brainstem symptoms such as vertigo, dysarthria, tinnitus, diplopia, bilateral paresthesias, decreased level of consciousness, or hypacusis. Onset is usually between ages 7 and 20 years and is more common in females. (See "Migraine with brainstem aura".)

●Hemiplegic migraine – The main feature of hemiplegic migraine is the presence of motor weakness as a manifestation of aura in at least some attacks. Besides weakness, the aura in hemiplegic migraine can include visual, sensory, and/or language disturbances. Severe episodes may also include fever, lethargy, coma, and seizures. (See "Hemiplegic migraine".)

OTHER TRANSIENT NEUROLOGIC EVENTS

Transient ischemic attack — The tissue-based definition of transient ischemic attack (TIA) is that of a transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction. This definition has replaced the older time-based one of focal neurologic symptoms or signs lasting less than 24 hours because even relatively brief ischemia can cause permanent neurologic or retinal injury.

●Typical TIA – Typical TIAs are characterized by transient, focal neurologic symptoms that can be localized to a single vascular territory within the brain, including one or more of the following:

•Transient monocular blindness (amaurosis fugax)

•Hemiparesis and/or hemisensory loss

•Aphasia or dysarthria

•Hemianopia

In most cases, the diagnosis of TIA is easily made based upon the clinical features, which involve negative features (ie, focal deficits). By contrast, epileptic seizures predominately involve positive ictal features (eg, involuntary movements and hallucinations) from neural hyperexcitability.

●Limb-shaking TIA – An exception is limb-shaking TIA, which is a rare hypoperfusion syndrome of repetitive jerking movements of the arm and/or leg due to a contralateral internal carotid artery stenosis or occlusion [71]. These can mimic focal motor seizures. Limb-shaking TIAs tend to have tremor-like movements that may be regular or irregular, sometimes provoked by movements that theoretically can exacerbate cerebral hypoperfusion, such as exercise or standing up from a bed or chair [71,72]. These shaking movements are often caused by a sudden loss of tone rather than a positive limb contraction.

The features of limb-shaking TIAs that help distinguish them from epileptic seizures include [72]:

•Preserved level of consciousness

•Absence of face or trunk involvement, tonic contractions, or march of symptoms

•Tendency to be provoked by movements that may reduce cerebral perfusion

Transient global amnesia — Transient global amnesia (TGA) is an uncommon, benign, self-limited, and relatively selective disturbance of anterograde amnesia that occurs in middle-aged and older adults. (See "Transient global amnesia".)

The event is characterized by a profound disruption in anterograde memory; patients are typically disoriented to place and will repeatedly ask where they are and why they are there, the so-called "broken record" phenomenon. Retrograde amnesia is variably present. There may be deficits in executive function, but most other cognitive functions are intact. Patients remain awake and alert and do not lose self-awareness. Physical or emotional triggers (eg, Valsalva maneuver, pain, stress, others) may precede the event. The episode gradually resolves within 24 hours or less (mean six hours). (See "Transient global amnesia", section on 'Clinical presentation'.)

TGA episodes last much longer (hours) than most seizures and are without lethargy or motor manifestations. Differentiating transient epileptic amnesia (TEA) from TGA can be difficult, but a hallmark of TEA is the recurrence of multiple, brief (typically minutes), stereotyped events and response to antiseizure medication. TGA must also be distinguished from dissociative amnesia, delirium, and stroke. (See "Transient global amnesia", section on 'Differential diagnosis'.)

CAA-related transient focal neurologic episodes — Patients with cerebral amyloid angiopathy (CAA) may present with transient focal neurologic episodes (TFNE), also known as amyloid spells, consisting of recurrent, brief, and often stereotyped spells of weakness, numbness, paresthesia, or other cortical symptoms that can spread smoothly over contiguous body parts over several minutes. (See "Cerebral amyloid angiopathy", section on 'Transient focal neurologic episodes'.)

TFNE can resemble other transient neurologic events including seizures. The symptoms of TFNE tend to localize to the site of a cortical subarachnoid hemorrhage, prior lobar hemorrhage, or focus of convexity superficial siderosis. A clinical feature more suggestive of TFNE than seizure is the smooth spread of the symptoms over minutes. However, the stereotypic recurrence of symptoms over time is a feature common to both entities.

The evaluation, diagnosis, and management of TFNE are reviewed separately. (See "Cerebral amyloid angiopathy", section on 'Transient focal neurologic episodes'.)

HALLUCINATIONS — 

Hallucinations are the perception of an external sensory stimulus where none exists. These can be somatosensory, visual, auditory, and olfactory.

Hallucinations can be part of a seizure aura (see "Focal epilepsy: Causes and clinical features") but can also occur as episodic phenomena in a variety of other conditions [73]. In general, these conditions can be distinguished from each other by the nature of the hallucination and accompanying clinical features.

An epileptic aura usually produces hallucinations that involve a single sensory modality or multiple sensory modalities that occur in sequence rather than simultaneously [74,75]. Olfactory hallucinations may be the best known, but they are actually less common than visual, somatosensory, and auditory auras [29,76]. While these hallucinations have some localizing value, they are not reliable in pinpointing the focus of seizure onset. (See "Focal epilepsy: Causes and clinical features".)

In general, epileptic auras are best distinguished from other causes of hallucinations by their paroxysmal onset, brevity (less than two minutes), and stereotyped recurrence. It is also unusual for a hallucination to be the sole manifestation of epilepsy in any given patient; these typically occur as seizure auras, followed by other ictal manifestations [74,75].

●Somatosensory hallucinations – Somatosensory or haptic hallucinations include external tactile sensations and internal bodily feelings. The former may be described as pain, itching, tingling, and electric shock sensations. Internal feelings include deep pain, nausea and other visceral sensations, and sexual pleasure. Patients may sense that a limb or joint is being moved when it is not.

Visceral hallucinations, such as the feeling of gastric rising, are a common aura in temporal lobe epilepsy (see "Focal epilepsy: Causes and clinical features", section on 'Neocortical temporal lobe epilepsy'). More superficial sensory symptoms of an epileptic aura tend to be lateralized. They may be stationary or they may "march" or spread over several seconds to a few minutes.

●Visual hallucinations – Visual hallucinations can be simple (eg, lights, colors, lines, shapes, or geometric designs) or complex (images of people, animals, objects, or a lifelike scene). They may be caused by a wide range of underlying etiologies, including retinal disorders, migraine, epileptic disorders, focal brain lesions, severely impaired vision, neurodegenerative disease (eg, dementia with Lewy bodies, Parkinson disease, Alzheimer disease), alcohol and drug use (table 7), psychiatric illness, and metabolic encephalopathy. The visual hallucinations of narcolepsy are complex images that occur immediately before falling asleep (hypnagogic) or just after awakening (hypnopompic).

The many causes of visual hallucinations are reviewed in detail separately. (See "Approach to the patient with visual hallucinations", section on 'Etiologies'.)

The etiology of visual hallucinations can generally be distinguished by specific clinical features including simple versus complex imagery, monocular versus binocular involvement, triggers, duration, insight, and associated symptoms and signs (table 8 and algorithm 1). (See "Approach to the patient with visual hallucinations", section on 'Diagnostic evaluation'.)

●Auditory hallucinations – Auditory hallucinations can also arise from injury to any portion of the peripheral and central auditory pathways. As with visual hallucinations, these may be simple and unformed (static, beeping, humming) or more complex (voices, music).

Auditory hallucinations are most strongly linked to schizophrenia, for which they are a core symptom, but they are also described in patients with Alzheimer disease and patients with epilepsy, as well as in otherwise healthy individuals [77,78]. (See "Schizophrenia in adults: Clinical features, assessment, and diagnosis", section on 'Hallucinations'.)

Schizophrenia and psychotic depression are usually associated with auditory hallucinations [79]. Distinguishing features of these hallucinations include their personal (often sinister) meaning for the patient, who usually lacks insight as to their unreal nature [80,81]. These hallucinations are less episodic and more prolonged than they are in other disorders. Patients generally have a clear sensorium (ie, they are awake and alert) and manifest other psychotic features (delusions and other abnormal thought content).

Auditory hallucinations are an uncommon manifestation of epilepsy (fewer than 2 percent of cases) [70,82,83]. Simple or unformed epileptic auditory auras or auditory distortions (hypacusis or hyperacusis) are often lateralized [84]. Complex, formed auditory hallucinations, such as voices or music, are less common and may be produced by seizures arising from the temporal association or limbic areas. These are often considered psychic rather than auditory because of associated experiential phenomena (eg, déjà vu) [70,74]. Musical hallucinations most often occur with nondominant hemispheric foci. Prominent auditory hallucinations are a feature of the genetic syndrome autosomal dominant epilepsy with auditory features (also called familial lateral temporal lobe epilepsy). (See "Focal epilepsy: Causes and clinical features", section on 'Genetic focal epilepsy syndromes'.)

●Olfactory hallucinations – Olfactory hallucinations are particularly associated with epilepsy but can also occur in neurodegenerative disease and in psychiatric conditions. When epilepsy is the cause, the seizure origin is in the temporal lobe. The hallucination is perceived as intense and foul but is often otherwise ill described. (See "Focal epilepsy: Causes and clinical features", section on 'Mesial temporal lobe epilepsy'.)

Dysosmia, an altered sense of smell, most often results from a local nasopharyngeal process such as toxin exposure, physical irritant, or medication effect. The abnormal smell perception may occur episodically when certain airborne aromatic molecules interact with injured receptors. As a result, dysosmia can appear unprovoked, random, and recurrent. As such, it may be reported as an olfactory hallucination [85]. (See "Taste and olfactory disorders in adults: Anatomy and etiology".)

●Multimodal hallucinations – Withdrawal states such as delirium tremens and intoxication with amphetamines, cocaine, phencyclidine, chloral hydrate, bupropion, or atropine can be associated with multimodality hallucinations [86]. These states may cause formication, a feeling of ants crawling under the skin, along with complex visual and auditory hallucinations. Patients usually exhibit agitation, confusion, and autonomic activity (tremulousness, tachycardia, diaphoresis).

SUMMARY

●Nonepileptic paroxysmal events – These are defined as sudden, episodic, involuntary changes in behavior, sensation, or consciousness that resemble epileptic seizures but are not accompanied by abnormal ictal discharges in the brain. The differential diagnosis of epileptic seizures in adolescents and adults includes a variety of benign, physiologic phenomena as well as pathologic conditions (table 1). (See 'Introduction and definition' above.)

●Syncope – Seizure and syncope are commonly confused as the cause of an isolated or episodic loss of consciousness, particularly when the episode is not witnessed. A careful history is important in distinguishing syncope from seizure. Key aspects of the history include the clinical setting, warning symptoms, associated symptoms, the quality of motor activity (if present), and the speed of recovery of consciousness. EEG is of limited utility unless an event is captured. (See 'Syncope' above.)

●Psychologic disorders – In this category, disorders that can mimic seizure include functional seizures, also known as psychogenic nonepileptic seizures (PNES); panic attacks; and episodic dyscontrol. (See "Functional seizures: Etiology, clinical features, and diagnosis" and 'Psychologic disorders' above.)

●Sleep disorders – Parasomnias, sleep-related movement disorders, and narcolepsy may be confused with epilepsy when events occur at night. Specific features of the events, including duration, frequency, timing, stereotypy, and vocalizations, can help distinguish nocturnal seizures from sleep disorders. (See 'Sleep disorders' above.)

●Movement disorders – These are rarely confused with seizures if the motor activity is classic in appearance and is sustained rather than episodic. However, movement disorders that present with episodic symptoms may be confused with focal epileptic seizures characterized by isolated dystonic posturing or continuous symptoms (epilepsia partialis continua). A video-EEG recording of events is invaluable in difficult cases. (See 'Movement disorders' above.)

●Migraine – Migraine and epilepsy share overlapping features. Both are characterized by episodes of neurologic dysfunction that may be accompanied by headache, as well as gastrointestinal, autonomic, and psychologic features. Motor activity and loss of consciousness are unusual for migraine and suggest epilepsy. (See 'Migraine' above.)

●Other transient neurologic events – Several conditions can cause transient neurologic deficits that may occasionally mimic seizure:

•Transient ischemic attack (TIA) – Typical TIAs are characterized by transient, focal neurologic deficits (negative symptoms) that can be localized to a single vascular territory within the brain. (See 'Transient ischemic attack' above.)

•Transient global amnesia (TGA) – This is an uncommon, benign, self-limited, and relatively selective disturbance of anterograde amnesia that occurs in middle-aged and older adults. TGA episodes last much longer than most seizures and are without lethargy or motor manifestations. (See 'Transient global amnesia' above.)

•Cerebral amyloid angiopathy (CAA)-related transient focal neurologic episodes (TFNE) – Also known as amyloid spells, TFNE consist of recurrent, brief, and often stereotyped spells of weakness, numbness, paresthesia, or other cortical symptoms that can spread smoothly over contiguous body parts over several minutes. (See 'CAA-related transient focal neurologic episodes' above.)

●Hallucinations – These can be part of a seizure aura but can also occur as episodic phenomena in a variety of other conditions. In general, these conditions can be distinguished from each other by the nature of the hallucination and accompanying clinical features. (See 'Hallucinations' above.)