8
CHAPTER
Differential Diagnosis
Pradeep Sahota
While the range of treatment options for managing seizures has improved significantly, newly diagnosed epilepsy continues to evoke concern in the mind of the patient as well as the family due to significant psychosocial, vocational, functional, and other implications. Given these concerns, it is important to make an accurate diagnosis of a seizure disorder and subsequently initiate the most appropriate treatment. To do so, seizure mimics must be ruled out. An improved understanding of both epileptic and nonepileptic disease processes has increased the possible differential diagnosis of spells (1–4). In addition, the development of better diagnostic methods (video EEG or vEEG monitoring, neuroimaging techniques) has expanded the ability to detect a range of seizure mimickers. Despite all these advances, the history obtained from the patient and observer remains vital to the diagnosis.
A variety of medical, neurological, and psychiatric conditions may mimic seizures and should be considered in the differential diagnosis of seizures. This chapter will focus on differential diagnosis of seizures.
CLINICAL PRESENTATION OF SEIZURES
A seizure may be defined as an event consisting of a paroxysmal, abnormal, excessive, disorderly neuronal discharge that may be accompanied by a variety of different clinical manifestations, depending on the site of origin, extent of neuronal involvement, and pattern of spread (5). Generalized seizures involve both hemispheres at the outset, whereas partial seizures start in a focal area. Hence, depending on the site of involvement and spread, almost any neurologic symptom or set of symptoms can be a manifestation of a seizure. These symptoms may include motor, sensory (somatosensory or special sensory), autonomic, and psychic manifestations, in addition to the loss or impairment of consciousness.
While the list of symptoms is broad, there are features that can cue clinicians toward the diagnosis of a seizure disorder. These include: history of prodromal symptoms, onset of symptoms, evolution of the event, and duration of the event (seconds to minutes, usually no more than a couple of minutes) and postevent features including focal weakness, confusion, and findings of tongue biting, and bladder-bowel incontinence. The stereotypical nature of these clinical manifestations is a salient feature of seizures. In addition, age of onset, knowledge of the precipitating factors, and relieving factors as well as the circumstances in which the events occur may be important.
A number of medical, neurological, and psychiatric disorders can have clinical presentations resembling those seen with seizures. Examples of medical disorders include syncope, cardiac disease, hypoglycemia, dizziness, and vertigo. Neurological disorders including transient ischemic attack (TIA), transient global amnesia, complicated migraine, movement disorders, and sleep disorders may also mimic seizures. Psychiatric disorders, including psychogenic nonepileptic seizures (PNES), anxiety or panic attacks, and certain physiological events such as hypnic myoclonus, may at times be also mistaken for seizures.
Given that the clinical presentations of seizures can vary widely based on the presence of motor, sensory and autonomic features, and impairment of consciousness, the differential diagnosis is best considered for each type of presentation. This approach is arbitrary but helps to differentiate seizures from other nonepileptic events based on the initial presentation with the caveat that some seizures may have a combination of motor, sensory, and other features.
Presentation With Motor Features
Both partial and generalized seizures can present with motor features. The movements may involve an extremity or all four extremities. They may be rhythmic and repetitive or organized and evolving. The movements can be tonic, clonic, myoclonic or semi-purposeful, versive eye movements with deviation of eyes to one side, or automatisms in the form of blinking, lip smacking, chewing, wringing or fumbling movements of the hands and extremities. The movements can evolve – starting with a tonic component and progressing to clonic activity. There may be vocalization or speech arrest. Usually, these findings are often stereotypical. They last seconds to minutes and rarely longer. Epilepsia partialis continua (EPC) is a unique condition where the movements can last up to days. The events may be preceded by aura (simple partial component) consisting of abnormal or unusual smell, taste, abdominal sensation. They may be followed by weakness of the involved extremity (Todd’s paralysis). Other clinical conditions that present with motor features include sleep disorders, movement disorders, TIA, hyperekplexia, and catatonia (Table 8.1).
TABLE 8.1 Differential Diagnosis of Seizures Presenting With Motor Features
Sleep disorders – night terrors, sleep walking, narcolepsy with/without cataplexy, REM behavior disorder |
Movement disorders – tics, paroxysmal nocturnal dystonia, nonepileptic myoclonus |
Transient ischemic attack/stroke |
Hyperekplexia |
Catatonia |
Psychogenic events |
Sleep Disorders
While seizures may occur at night, occasionally other sleep disorders may present a diagnostic challenge and may need to be distinguished from seizures. These include night terrors, sleep walking, rapid eye movement (REM) behavior disorder (RBD), and narcolepsy with/without cataplexy.
Night terrors are usually seen in children and consist of sudden awakening from sleep with loud crying. The child appears to be in a state of fear and shock and is confused and almost inconsolable. He or she is unable to follow the commands of the parents or caregiver. The event lasts several minutes before the child is able to fall back to sleep. It can be distinguished from nightmares, as there is no dream phenomena associated with it. These events occur in stage III sleep.
Sleepwalking (like night terrors) is also frequently seen in children and tends to resolve by the late teenage years. The episodes of sleepwalking consist of the patient getting out of bed and walking around the house or sometimes even opening the door and walking outside. The event may last several minutes. Again, there are no accompanying dream phenomena and the patient usually does not have any recollection of the episode later on. Sleepwalking also occurs during stage III sleep.
RBD is characterized by vivid dreams with dream enactment (6). Depending upon the dream content, the accompanying behaviors may involve vocalizations, organized movements, or dangerous violent manifestations. In comparison with night terrors and sleepwalking, these episodes occur during REM sleep. An overnight polysomnogram (PSG) may reveal significantly increased muscle tone during REM sleep and dream enactment motor behavior, should the patient happen to have one of these episodes during the night of the recording. The disorder may be idiopathic or may occur in the setting of a variety of synucleonopathies. In fact, the disorder may predate the onset of other recognized symptoms of these degenerative neurological disorders.
Narcolepsy is characterized by excessive daytime sleepiness and sleep attacks. Sleep attacks represent acute onset of sleep, can be brief (microsleep), and may contribute to automatic behavior. Cataplexy is the acute, brief, partial, or complete loss of muscle tone usually precipitated by emotions. The acute paroxysmal nature of the presentation of narcolepsy/cataplexy may be confused with seizures as the patient has sudden loss of tone and often falls down during the cataplexy events. During these events the patient is conscious and aware unless sleep follows. An overnight PSG followed by multiple sleep latency test (MSLT) is helpful for diagnosing narcolepsy. Low cerebrospinal fluid (CSF) hypocretin level may be diagnostic, but the need for spinal fluid sampling and its limited availability makes this an uncommonly employed test.
Movement Disorders
Most movement disorders are chronic disorders that may be persistent or progressive and are usually easy to distinguish from seizures. However, some movement disorders are episodic or paroxysmal.
Tics or habit spasms are spontaneous, purposeless movements with the associated urge to execute the tic and transient relief afterward. Movements include blinking, eye movements, shoulder shrugging, head-nodding, sniffing, or throat clearing, and may occur in isolation or constitute a sequence of movements without any accompanying neurological deficits.
Paroxysmal dyskinesias consist of dystonic posturing, chorea, athetosis, and hemiballismus that can be unilateral or bilateral and may affect one region of the body or may be generalized. For instance, nocturnal paroxysmal dystonia is characterized by bursts of generalized choreo-athetotic, ballistic, and dystonic movements occurring during non-REM sleep (7). However, there have been reports of brief episodes of nocturnal paroxysmal dystonia lasting less than a minute in which vEEG monitoring showed evidence of frontal lobe epilepsy (8). Longer-lasting episodes spanning several minutes with no associated EEG abnormalities are thought to be nonepileptic.
Nonepileptic myoclonus consists of isolated jerky movement without any accompanying electrographic epileptiform abnormalities. It can arise from several foci in the central nervous system including the spinal cord or brainstem. A common form is hypnic myoclonus, which are isolated myoclonic movements during transition to sleep.
Transient Ischemic Attack
TIAs are characterized by acute onset of weakness, numbness, language difficulty, gait difficulty, or loss of vision. They are acute in onset and consist of loss of motor or other functions rather than abnormal movements that are uncommon. Rarely nonrhythmic involuntary movements of the involved extremity can be seen in carotid artery TIAs. Posterior circulation TIAs may be accompanied by acute vertigo, double vision, blurry vision, dysarthria, and ataxia. TIAs usually last longer than seizures (most events last less than 30 minutes, though by definition can last up to 24 hours). They may occur in patients with known cerebrovascular disease or may be the initial presentation. Hence, it should be noted that TIAs may be the warning signs of future strokes and should be carefully evaluated. Stroke has longer-lasting motor, sensory, language, or other deficits. Acute confusional states have been reported with cases of right middle cerebral artery strokes (9).
Hyperekplexia
Hyperekplexia represents exaggerated startle response, often noted to start in infancy, that may lead to a fall. This condition needs to be distinguished from startle-induced epileptic seizures (10) that may consist of noise (or other somatosensory or visual stimuli) that may induce asymmetric tonic posturing (11).
Catatonia
Catatonia is seen in patients with schizophrenia. It consists of tonic posturing with a tendency to tonically maintain the extremity in a given position, sometimes referred to as waxy flexibility. It can be seen in other conditions such as Down syndrome and Prader-Willie syndrome.
Presentation With Sensory Features
Partial seizures may be associated with sensory or special sensory features. These can include abnormal smell, taste, visual imagery (including formed images such as faces, scenes, or unformed lights or colors), feelings of strange familiarity (déjà vu), epigastric/abdominal sensations, feelings of dizziness or vertigo, and somatic sensations involving the extremity or extremities. Other clinical conditions that present with sensory features include TIAs (discussed earlier), migraines, hypnagogic hallucinations, paroxysmal painful episodes, and transient paresthesias (Table 8.2).
Migraine
Classical and complicated migraines may have transient neurological features that mimic seizures. Classic migraine usually consists of a visual aura in the form of a scintillating scotoma that evolves over several minutes. There may be other transient sensory symptoms. While stereotypical in nature, the presence of the visual aura followed by a severe headache with much slower evolution of symptoms taking several minutes distinguishes a migraine headache from a seizure. Confusional migraine may have an additional component of mental status change. Complicated migraines may be accompanied by neurological deficits like lateralized weakness, referred to as a hemiplegic migraine. The weakness can be ipsilateral or contralateral to the side of the headache. The events are also stereotypical in nature, but last much longer (though postictal paralysis following a seizure can last minutes to hours or longer as well), and usually there is a family history of migraines.
