Paroxysmal dyskinesia lies squarely in the borderland between epilepsy and movement disorders. Prior to Mount and Reback's paper in 1940 (141), describing familial paroxysmal choreoathetosis, most authors described these disorders as unique forms of epilepsy with names like extrapyramidal epilepsy (142), reflex epilepsy (143,144), striatal epilepsy (145), and subcortical epilepsy (146). Although there is still some controversy, a growing consensus believes that paroxysmal dyskinesias are nonepileptic in nature.

The most common and most well described paroxysmal dyskinesia is paroxysmal kinesigenic choreoathetosis (PKC). It is characterized by brief, jerky, choreiform, or dystonic movements lasting seconds to minutes that are provoked by voluntary movement or startle (147). PKC may be inherited or sporadic, with sporadic forms dominating in the United States. In contrast, a Japanese paper reported that 97 of 150 cases were inherited (148). Autosomal dominant forms have been localized to chromosome 16p11–q12 (149), and a second locus has been described at chromosome 16q13 (150).

PKC also may be secondary to other disorders including multiple sclerosis (151), stroke (152), HIV (153), hypoparathyroidism (154), hyperthyroidism (155), and it may be psychogenic (156).

Primary PKC usually begins in childhood, with peak activity during adolescence resulting in up to 100 attacks a day. Some patients describe a sensory pro-drome of dizziness, muscle tension, tingling, or numbness, although neurologic examination between attacks is usually normal. MRI (157), EEG, and autopsy results (158,159) are generally unrevealing. Nagamitsu et al. reported a large study with eighty-four of one hundred patients with a normal "interictal" EEG and twenty-nine of thirty-one patients had no EEG changes recorded during an attack (148). Interestingly, SPECT scanning has demonstrated an increased perfusion of the contralateral basal ganglia during attacks (157).

The disease is nonprogressive and treatment with antiepileptic medications, especially carbamazepine (160,161), phenytoin (147), and more recently, oxcar-bazepine (162) and lamotrigine (163) is often effective.

In contrast to PKC, in paroxysmal nonkinesigenic choreoathetosis (PNKC), the attacks are not stimulated by movement. However, they may be triggered by stress, sleep deprivation, caffeine, alcohol, or tobacco use. Attacks in PNKC are longer, lasting minutes to hours. Dystonic posturing in PNKC may be uncomfortable, and generally occur less frequently than attacks of PKC, at most a few times a day. Speech may be affected during attacks of PNKC and this may be misinterpreted as a change of mental status, thus resulting in further confusion with epilepsy.

Similarly to PKC, there are genetic forms with autosomal dominant inheritance, in this case localized to chromosome 2q (164). However, most forms of PNKC are sporadic or symptomatic, with a panoply of causes including multiple sclerosis, trauma, stroke, HIV, metabolic derangements, hypoparathyroidism, hyper-thyroidism, and psychogenic etiologies (165).

Analogous to PKC, diagnostic investigations in PNKC including CT and MRI, CSF, EEG, autopsy, "non-ictal" PET scans, and "ictal" MR single positron emission computed tomography (SPECT) scans are all without findings (166–169).

The second major difference of PNKC is that the syndrome is quite refractory to therapy. Clonazepam may be partially effective, and acetazolamide, anticholinergics, and haloperidol have been useful in individual cases (168,170). Recently, however, some hope has arisen for the efficacy of alternate-day oxazepam (171) as well as gabapentin (172). Interestingly, both phenytoin and levodopa have been shown to worsen episodes (171).

Paroxysmal exercise-induced dystonia or intermediate paroxysmal nonkinesigenic dystonic choreoa-thetosis is a disease similar to PKC, with episodes lasting longer and induced by extended exercise. There are reports of both familial and sporadic forms (173–175). Paroxysmal ataxia exists as both familial forms, some with concurrent nystagmus or myokymia (176), and those due to metabolic defects including Hartnup's disease (158), pyruvate decarboxylase deficiency, and maple syrup urine disease (177).

Although the differentiation of these syndromes is often difficult, the diagnostic challenge is further increased by their overlap with epilepsy. Demirkiran et al. found a frequent family history of idiopathic epilepsy in patients with paroxysmal dyskinesias, and Tan et al. reported a series of cases showing 8% of patients to have both epilepsy and PKC (178). However, the clinician is aided by the nature of the movements, absence of loss of consciousness or generalization, and normal imaging and EEG.