As early as the late nineteenth century, neurologists noted overlap between certain movement disorders and epilepsy. This is perhaps most apparent in patients with myoclonus, as discussed in the preceding chapter in this book. Many patients afflicted with chronic myoclonus also have epilepsy, and forms of focal epilepsy can precisely mimic myoclonus. Most of the drugs effective at treating myoclonus (clonazepam, valproic acid, levetiracetam, zonisamide, acetazolamide) are antiepileptics. Besides myoclonus, there are other disorders that occur in brief or sustained paroxysms, without alteration in arousal or consciousness; these disorders are the subject of this chapter. Often these patients are referred for evaluation to epileptologists or movement disorder specialists. Video-electroencephalogram (EEG) monitoring may be necessary to rule out an epileptic cause, although most of these disorders can be recognized once the physician is familiar with the syndrome.

Several paroxysmal movement disorders that may be confused with epilepsy are considered elsewhere in this book. Myoclonus, as mentioned previously, is the closest mimic. Patients with hyperekplexia have an inherited disorder of exaggerated startle and sustained tonic contractions due to mutations in the glycine receptor. These patients usually present in the nursery with exaggerated startle, abnormal tone, and lack of habituation to startle. Recognition is critical because appropriate treatment with clonazepam prevents potentially life-threatening apneic episodes. Paroxysmal torticollis is another disorder beginning in early childhood, with episodes of sustained tonic contraction of neck muscles producing sustained head postures for hours or days. Events typically occur periodically, and alertness and arousal are preserved. This migraine variant is also usually easily distinguished from epilepsy. Infants may sometimes evidence paroxysmal, brief episodes of upward gaze, so-called tonic upgaze of infancy, which may raise the notion of epilepsy. These episodes are brief, typically last seconds, are unassociated with other abnormalities, and, although they are disconcerting to parents, usually disappear by early childhood.

Four other movement disorders mimicking epilepsy are considered further in this chapter: (a) stereotypies (complex tics), (b) episodic ataxia, (c) self-stimulatory behavior, and (d) the paroxysmal dyskinesias.

Stereotypies are highly patterned, complex, sustained movements, often lasting seconds, which are typically repeated multiple times. Examples of stereotypic movements include truncal rocking, skin picking, hand clapping, hand twirling, and complex hand-to-mouth routines (feeding, blowing, touching). Phenomenologically, there is little difference between a complex motor tic, that is, a complex sequence of involuntary movements performed in response to an inner urge, and stereotypies. Stereotypies are most commonly seen in patients with autism, pervasive development delay, and Asperger syndrome, but they may also occur in developmentally disabled individuals, in Rett syndrome, and in otherwise normal children.^19,45,87,116 Because these events are brief, involve complex involuntary movements, and may affect patients’ ability to interact with the examiner, they may be mistaken for supplementary motor area seizures. It is not uncommon for video-EEG monitoring to be ordered to differentiate long-duration stereotypies from seizures, particularly when they occur in neurologically abnormal individuals.

Episodic ataxia is a rare, genetic paroxysmal movement disorder that should be easy to distinguish from epilepsy. The disorder occurs in two forms, types 1 and 2. Episodic ataxia type 1 is an autosomal-dominant disorder characterized by paroxysms of ataxia lasting several minutes, often with myokymia between attacks. The disorder has been linked to mutations in the voltage-gated K⁺ channel gene, KCNA1.^14,27,48 Episodic ataxia type 2 is an autosomal-dominant disorder characterized by paroxysms of ataxia lasting hours, often with interictal symptoms of nystagmus or cerebellar dysfunction. The disorder is linked to mutations in the alpha 1A voltage-dependent calcium channel subunit, CACNA1A. Acetazolamide and 4-aminopyridine have been shown to be beneficial in affected patients.^{59,60,125,128}

Self-stimulatory behavior is not infrequently encountered at centers that perform video-EEG monitoring. This condition typically begins in early childhood, affects girls more than boys, and is usually first noticed by parents. In a typical event the child crosses his or her legs, lies flat on the floor, or applies pressure to the groin or perineum against furniture. Children can be distracted during an episode, and there may be accompanying autonomic signs such as facial flushing or sweating. Videorecording is extremely useful in documenting the nature of these events. If the clinical appearance is classic, investigative studies are unnecessary. The term “infantile masturbation” should be avoided when discussing this condition with parents because there is significant stigma associated with it. We have encountered parents who refuse to accept this diagnosis, persisting in extensive evaluations to prove a different etiology for the condition. Most children respond to redirection and support.^{32,96,103,149}

In the remainder of this chapter, we discuss the paroxysmal dyskinesias, a complex and unusual group of disorders that bear relation to epilepsy. Because the literature of paroxysmal disorders is extensive and often confusing, we first offer a historical review of the development of these disorders and then present current concepts related to their nosology and etiology.

Gowers⁴⁴ was probably the first to report “movement-induced seizures,” in this case, in an 11-year-old girl who developed brief attacks that occurred when she suddenly arose after prolonged sitting. Numerous reports of “movement-induced seizures” followed, published under the designations of ref- lex epilepsy or tonic seizures induced by movement. Some cases
demonstrated more than tonic contractions—namely, sustained twisting, athetosis, and chorea. Even the presence of choreoathetosis, however, did not lead the earliest interpreters of these brief attacks to conclude that they represented a movement disorder. Rather, they considered them to be a form of epilepsy, with the cerebral site of the “seizures” in the basal ganglia or subcortical region.

After Gowers, the next report of movement-induced paroxysmal movements appears to be that of Spiller in 1927.¹²⁶ He described two patients with brief tonic spasms brought on by voluntary movement of the involved limbs, and in one of them by passive manipulation. Contractions were painful and accompanied by sensations of heat or burning. Wilson¹⁴⁵ later described a 5-year-old boy who had brief attacks of unilateral torsion and tonic spasm that lasted up to 3 minutes and were precipitated by pain. Wilson considered this to be reflex tonic epilepsy, and also thought it to be subcortical in origin.

The concept of attacks of tonic, often twisting, contractions without loss of consciousness as uncommon seizure disorders continued. Lishman et al.⁸⁰ described seven patients with tonic and athetoid spasms induced by movement while remaining conscious. Abnormal sensations of numbness, vibration, and tightness were noted in the affected limbs before the attacks. Two years later they reported an additional five cases of movement-induced “seizures,”¹⁴³ and Burger et al.¹⁵ described two patients with this label. Some also referred to these cases as forms of epilepsy.^38,52

In 1940, Mount and Reback⁹⁹ introduced a new concept—attacks of tonic spasms plus choreic and athetotic movements with unusual triggers. They described a 23-year-old man who had had “spells” since infancy, both “large” and “small.” Both types were preceded by a sensory aura of tightness in parts of the body or by a feeling of tiredness. Movements involved the arms and legs, usually a combination of sustained twisted posturing and chorea. The “small” attacks lasted from 5 to 10 minutes; longer attacks were considered “large” and also involved the neck (retrocollis), eyes (upward gaze), face (ipsilateral to the limbs, if the limb involvement was unilateral), and speech. These “large” attacks lasted for as long as 2 hours. Drinking alcohol, coffee, tea, or cola would usually precipitate an attack, as would fatigue, smoking, and intense concentration. The attacks cleared more rapidly if the patient lay down, and they were aborted by sleep. Between attacks, the neurologic examination was normal, and there was never loss of consciousness, clonic convulsive movements, biting of the tongue, or loss of sphincter control. Phenytoin and phenobarbital were without effect, and scopolamine was the only drug found to reduce the frequency, severity, and duration of attacks. The family history revealed 27 other members with similar attacks, with a pedigree showing autosomal-dominant inheritance with complete penetrance. Mount and Reback called this disorder familial paroxysmal choreoathetosis.

This paper by Mount and Reback became the seminal report in the field of paroxysmal dyskinesias. After its publication, it was referenced by most reports in the literature over the next five decades, although the next report of a large family with similar attacks of muscle spasms did not reference it. In 1961 Forssman³³ described a family whose members had attacks lasting from 4 minutes to 3 hours; inheritance was autosomal dominant. Attacks were induced by cold, mental tension, irritation, fatigue, lack of sleep, alcohol, and caffeine. Onset of symptoms was in early childhood; an attack might begin with a tonic spasm in one hand and spread up the arm to the other arm, to both legs, and then to the cranial muscles, including the tongue, so that the affected person could not speak during a severe attack. Forssman considered the disorder to be new, possibly related to myotonia and paramyotonia, and did not consider it a form of epilepsy because no alteration of consciousness was involved.

In 1963, Lance⁷³ reported eight similar patients with attacks of tonic (dystonic) spasms, some with choreoathetosis, usually affecting only one side of the body and often preceded by pain or tingling. Two patients had secondary attacks (static encephalopathy and multiple sclerosis), one case was idiopathic and sporadic, and the remaining five were members of the same family. The attacks lasted <1 minute in two patients, 2 to
5 minutes in the patient with multiple sclerosis, and 5 to 60 minutes in the five familial cases. They were not precipitated by movement, and the familial cases were exacerbated by excitement and fatigue. No EEG abnormality was recorded between attacks.

After the 1963 article by Lance,⁷³ Weber¹⁴² reported a family of four affected members with nonkinesigenic paroxysmal dystonia and used the term familial paroxysmal dystonia. Richards and Barnett¹¹⁴ reported the next big family with the same type of paroxysmal dyskinesia as Mount and Reback’s and thought that Lance’s family⁷³ represented a variant because its members had only tonic spasms and no movements. The family of Richards and Barnett consisted of nine affected members with the trait inherited in an autosomal-dominant pattern. They emphasized the nonkinesigenic nature of the attacks and felt that a wide array of terms could describe the attacks, depending on the severity of each one. Richards and Barnett coined the term paroxysmal dystonic choreoathetosis (PDC), which was later adopted by Lance in 1977.⁷⁴ The terms paroxysmal nonkinesigenic choreoathetosis and paroxysmal dystonia were sometimes used instead of PDC.¹² The term paroxysmal nonkinesigenic dyskinesia (PNKD), proposed by Demirkiran and Jankovic,²³ is currently the accepted designation for this syndrome (Table 1).

In 1967, Kertesz⁶⁵ introduced the label paroxysmal kinesigenic choreoathetosis (PKC). This label developed into a most useful and widely accepted designation. Kinesigenicity has an important place in the classification of the paroxysmal dyskinesias, and Demirkiran and Jankovic²³ recommended that the term paroxysmal kinesigenic dyskinesia (PKD) be used instead because movements can be dystonic, choreic, or a combination of the two. Rarely, the PKD designation can be applied to certain patients whose dyskinesias are not triggered by sudden movement (or startle).

In his paper, Kertesz reported 10 new cases of paroxysmal dyskinesia and reviewed the literature. It is significant that he differentiated the kinesigenic variety from the cases described by Mount and Reback, Forssman, and Lance, which were not exacerbated by movement but by alcohol, caffeine, or fatigue. Although phenytoin was recognized earlier as a very useful agent for PKD, carbamazepine was later found to be equally useful and was introduced as a treatment by Kato and Araki.⁶⁴

The original cases reported as PNKD were idiopathic and usually familial. It was not long before symptomatic cases began to be reported in patients with perinatal encephalopathy,¹¹⁹ encephalitis,¹⁰⁰ head injury,^117,144 as a manifestation of multiple sclerosis,^61,90,136 and idiopathic hypoparathyroidism.²

The next major advance in classification was by Horner and Jackson,⁵⁴ who described two families in which several members had attacks of involuntary movements that occurred during sleep. These appear to be the first reported cases of hypnogenic paroxysmal dyskinesia. In one family, some of the affected members had classic paroxysmal kinesigenic dyskinesia, some hypnogenic, and others a combination of the two. Case 3 in this family began with the hypnogenic variety when the patient was 8 years old. By the time he had reached the age of 11 years, daytime attacks were also occurring, sometimes triggered by sudden movement. The hypnogenic episodes gradually disappeared, leaving him with kinesigenic dyskinesia that responded to antiepileptic drugs.

Lugaresi and colleagues^83,84 independently rediscovered and eventually made known the syndrome of hypnogenic paroxysmal dyskinesia. Lugaresi and Cirignotta⁸⁴ described five patients with onset of hypnogenic dystonia at ages 5, 7, 26, 30, and 40 years. Attacks occurred almost every night during sleep, with onset in stages 2 to 4 of sleep. They lasted 15 to 45 seconds and might recur several times in the same night. They could awaken the patient, who might even emit a cry. The movements appeared to be a mixture of dystonia, athetosis, and some more rapid flinging movements. The EEG findings were normal during sleep and wakefulness. Carbamazepine was effective. In their article, Lugaresi and Cirignotta described the movements as choreoathetosis and ballism in addition to dystonia. Maccario and Lustman⁸⁵ emphasized that tachycardia is a characteristic occurrence during these episodes.

The disorder was originally described in nonfamilial cases but was later reported in three members of a family.⁷⁵ Other sporadic cases have been reported as well,^{21,41,113,132} including one with a concurrent reflex dystonic reaction provoked by stimulation of the right foot.⁷⁷ Another link with PKD is suggested by the report of Morley,⁹⁸ who described a father with hypnogenic dyskinetic attacks and a son with PKD. Both responded to phenytoin.

There has long been considerable speculation as to whether the short-duration hypnogenic attacks might be a manifestation of epilepsy because they respond so well to antiepileptic drugs. The lack of abnormal EEG findings during these attacks has been used to argue against this concept. However, evidence accumulated that many hypnogenic paroxysmal dyskinesias are, indeed, caused by seizures. Tinuper et al.¹³³ described three patients with this disorder who had EEG evidence of frontal lobe seizures as a cause of their attacks. Sellal et al.¹²¹ and Meierkord et al.⁹² studied a series of patients with hypnogenic dystonias and concluded that they represent seizure disorders, particularly of frontal lobe epilepsy, because repeated nocturnal EEG recordings often reveal epileptic patterns of abnormalities. Seizures arising near the mesial posterior frontal supplementary sensorimotor area (SSMA) may be a particular culprit in inducing paroxysmal hypnogenic dyskinesias in children.⁵ These types of seizures tend to be brief, frequent, and associated with bilateral tonic posturing, gross proximal limb movements, and preserved consciousness. Dystonic and other dyskinetic features may result from spread of epileptic activity from the mesial frontal region to the basal ganglia because the anatomic connections between these areas are close. The subject of epilepsy masquerading as a movement disorder has been reviewed by Hirsch et al.⁵¹ and Fish and Marsden.³¹

Although most patients with paroxysmal dyskinesias fit into one of these classification schemes, it has become clear that some patients defy easy classification. Several patients have been reported with both nocturnal and daytime paroxysmal events without EEG correlate. Daytime attacks may be triggered by movement or may sometimes occur without trigger.^22,111 Results of imaging and EEG monitoring are usually not helpful, and patients are often difficult to treat.