Clinical Features and Classification

The primary finding associated with paroxysmal dyskinesia is sudden, transient attacks of chorea, athetosis, dystonia, ballismus, or any combination of these abnormal movements involving muscle groups of the arms, legs, trunk, face, and/or neck. These episodes may be relatively short- or long-lasting in duration and occur spontaneously or be brought on by sudden voluntary movement, stress, fatigue, caffeine, alcohol, heat, cold, prolonged exertion, sleep, or other factors. Following is a more in-depth description of these paroxysmal movement disorders, including some rare disease variants that have been described in the medical literature.

Paroxysmal kinesigenic dyskinesia (PKD)
Previously designated as "paroxysmal kinesigenic choreoathetosis" (PKC), the term "paroxysmal kinesigenic dyskinesia" is now considered more appropriate since the episodes are often not witnessed and therefore the movement disorder cannot be classified into choreic, athetotic, ballistic, or dystonic. In many patients with PKD, particularly those with idiopathic (i.e., familial or sporadic) disease, symptom onset is before age 20, usually during childhood. However, the age at onset may vary, ranging from about 6 months to 40 years in familial cases, but the age at onset may be considerably later in secondary (symptomatic) cases. While many reports have concluded that males are affected more frequently than females by idiopathic (familial and sporadic) PKD, a recent report that primarily included idiopathic sporadic and secondary cases indicated that males and females appear to be affected relatively equally.

The transient attacks associated with PKD primarily affect muscles of the arms and legs; however, muscles of the face, neck, and/or trunk may also be involved. PKD episodes may affect muscle groups on one (unilateral) or both sides (bilateral) of the body, but even if bilateral they are usually asymmetrical. Involvement of facial or oromandibular muscles often results in transient facial grimacing, difficulties speaking (dysarthria), or even muteness; however, the episodes are not accompanied by altered consciousness. When leg and trunk muscles are affected, falls may occur, causing a risk of injury. PKD may interfere with walking or standing or conducting other activities of daily living (ADLs), potentially resulting in severe disability.

In addition to sudden movement, some episodes may also be provoked by unexpected stimuli (startle), yawning, talking, hyperventilation, the anticipation of movement, or light (photic) stimulation. Attacks may be worsened by certain factors, such as stress, cold, heat, or menstruation.

Most patients with PKD experience daily episodes. The frequency of attacks ranges from as few as 1 each month (or less) to as many as 100 each day. Before the onset of such episodes, some patients may experience unusual warning or "premonitory" sensations, such as prickling, tingling, or crawling (paresthesias); dizziness; or muscle tension. Such abnormal sensations usually involve the affected region. The frequency of PKD episodes usually decreases with age.

Generally, most patients with PKD have brief attacks lasting from seconds up to 5 minutes. However, some rare cases have been reported in which kinesigenic episodes may have a duration of more than 5 minutes up to hours. According to some reports, long-lasting PKD appears to be associated with an older age at symptom onset than that seen with short-lasting PKD; in addition, short-lasting episodes seem to occur more frequently than long-lasting attacks. It is also important to note that, in some patients with PKD, the length of attacks may change over time from short- to long-lasting or vice versa.

Paroxysmal non-kinesigenic dyskinesia (PNKD)
In many individuals with paroxysmal non-kinesigenic dyskinesia (PNKD), symptoms become apparent before age 20. However, the age at onset may be extremely variable and the symptoms may not become manifested until 40 years of age or even later. Males appear to be more frequently affected by PNKD than females, but some series have not found a male preponderance.

Phenomenologically, PNKD is similar to PKD, except for the precipitating factors. This paroxysmal movement disorder was previously categorized as "paroxysmal dystonic choreoathetosis" (PDC). However, the term "paroxysmal non-kinesigenic dyskinesia" has since been recommended to more appropriately imply the larger spectrum of hyperkinetic movements potentially associated with the disease. As with PKD, PNKD attacks may be associated with any combination of various movement abnormalities, including chorea, athetosis, dystonic posturing, and ballismus. It is again important to emphasize that the episodes are not accompanied by an altered state of consciousness. Attacks may be so severe that they result in sudden falls or significantly interfere with walking, standing, or performing other activities of daily living (ADLs), potentially resulting in severe disability.

PNKD episodes may occur spontaneously without any specific "triggering" factors. However, episodes may be worsened by stress, anxiety, or excitement; fatigue; heat or cold; consumption of alcohol; intake of caffeine, such as in coffee, tea, or chocolate; fasting; or other factors.

The frequency of PNKD episodes is typically lower than that associated with PKD, ranging from approximately 2 to 3 per month up to about 20 per day; most patients with PKD experience daily attacks (up to 100 per day). In some patients, unusual "foreboding" sensations may occur prior to PNKD episodes. These may include prickling, crawling, or tingling sensations (paresthesias) or muscle tension in the affected region. As with PKD, PNKD attacks tend to decrease with age.

In contrast to usually brief episodes of PKD, the PNKD attacks last longer (from approximately 5 minutes up to about 4 hours or, sometimes, up to 2 days), although cases of PNKD have been reported in which non-kinesigenic episodes have a short-lasting duration of about 10 to 30 seconds (less than 5 minutes) . Thus, similar to PKD, PNKD is further classified based upon the duration of episodes into "short-lasting" (less than or equal to 5 minutes) or "long-lasting" (longer than 5 minutes). As with PKD, there have also been reports in which some patients with PNKD have experienced a change in the length of episodes from long- to short-lasting or vice versa. In addition, long-lasting PNKD appears to be associated with a younger age at symptom onset than that seen with short-lasting PNKD.

Paroxysmal exertion-induced dyskinesia (PED)
A relatively rare form of paroxysmal dyskinesia has been described in which episodes are induced by prolonged exertion. Previously categorized as "intermediate PNKD," this variant is currently classified as "paroxysmal exertion-induced dyskinesia" (PED) specifically based upon the precipitant rather than the duration of the attacks.

In patients with idiopathic (familial or sporadic) PED, symptoms typically become apparent during childhood. In the only recorded case of secondary (symptomatic) PED, the age at onset was 29 years. In those with familial PED, females appear to be affected more frequently than males. However, in idiopathic sporadic PED, females and males are affected relatively equally.

PED is primarily characterized by sudden, transient, dystonic attacks, associated with involuntary, repetitive, twisting motions and distorted, often painful posturing. In some patients, attacks of dystonia may be accompanied by irregular jerky movements (chorea) and relatively slow, writhing movements that appear to flow into one another (athetosis). Such episodes are brought on by strenuous activity or prolonged exertion, such as running or walking for approximately 5 to 15 minutes. A few cases have also been reported in which PED attacks are provoked by passive movements of affected limbs. Episodes may be worsened by certain factors, including stress, cold, or menstruation. PED attacks primarily involve the legs or feet. However, muscles of the arms, face, neck, and/or trunk may sometimes be involved in those with short-lasting PED episodes (see below). Although muscle groups are often affected on both sides of the body (bilateral), only one side (unilateral) may be involved in some patients. Unlike PKD and PNKD, patients with PED usually do not experience any premonitory sensations prior to the onset of PED attacks.

Most patients with PED have about 1 to 5 episodes per month. However, some may experience up to 1 to 2 attacks daily. PED episodes usually have a duration ranging from about 5 to 30 minutes. Yet a few cases have been reported in which episodes were short-lasting, with a duration of seconds up to 2 minutes. In addition, in one family originally classified as having PNKD who had episodes precipitated by prolonged exertion, some affected members experienced both short- and long-lasting attacks: episodes lasted for a few seconds up to about a minute or as long as up to 2 days. Reports suggest that long-lasting PED episodes appear to be more common in younger individuals.

Paroxysmal hypnogenic dyskinesia (PHD)
Paroxysmal hypnogenic dyskinesia or PHD, a rare disease variant, is characterized by transient attacks of involuntary movements occurring during non-REM (NREM or non-rapid eye movement) sleep. In rare instances, PHD episodes may be preceded by premonitory, potentially painful sensations. In addition, the attacks are often preceded by signs of awakening (arousal). During PHD attacks, the eyes may open and there may be abnormal, involuntary, potentially violent movements of the arms, legs, and trunk. These may include uncontrollable flinging or throwing movements of the arms and legs (ballismus); excessive rigidity, with associated, repetitive, twisting motions and distorted, potentially painful posturing (dystonia); and irregular jerky motions (chorea) and relatively slow, writhing movements that appear to merge into one another (athetosis). In some instances, the attacks may be associated with additional findings, including involuntary utterances (vocalizations), irregular breathing patterns, or an accelerated heart rate (tachycardia). Although patients usually fall asleep after PHD episodes, they typically remember the attacks. Episodes may be worsened by certain factors, such as fatigue, stress, increased activity, or menstruation.

Idiopathic (familial or sporadic) PHD usually becomes apparent during childhood. Reports suggest that familial PHD typically has a younger age at symptom onset than sporadic disease. Based upon various reports, the age at onset may range from about 2 to 23 years in familial cases and approximately 3 to 47 years in idiopathic sporadic cases.

In some patients, PHD attacks may initially occur approximately 4 to 5 times each year. Over time, however, the frequency of episodes may increase up to 4 to 5 times nightly. The attacks are usually relatively brief, ranging from about 20 to 50 seconds or up to approximately 2 minutes. However, in some patients, episodes may have a longer duration of more than 5 minutes up to about 50 minutes.

In some instances, patients may experience nocturnal episodes as well as daytime kinesigenic or non-kinesigenic attacks. In addition, in some affected families (kindreds), different members may have different forms of paroxysmal dyskinesia.

	Genetics