Historical Background

• The first known description of paroxysmal kinesigenic dyskinesias (PKD) was by Shuzo Kure (1892) detailing a Japanese man with PKD.
• Initial reports often regarded PKD as a form of reflex epilepsy.
• Currently it considered as one of the three categories of paroxysmal dyskinesias, the other two being paroxysmal non-kinesigenic dyskinesia (PNKD), and paroxysmal exercise-induced dyskinesia (PED) (Jankovic J & Demirkiran M, 2002).

Clinical Features

• Lishman et al. (1962) provided a thorough and beautifully written account of PKD's clinical characteristics while describing seven patients.
• Attacks usually begin in childhood and occur frequently.
• Precipitated by sudden movement, often after a period of rest.
• Movement of the legs is more likely to initiate attacks than the arms.
• An element of surprise or "startle" is important; tension, anxiety, or self-consciousness increases the likelihood of attacks.
• Subjective preparation for movement and slow initiation of action tend to reduce or abort attacks.
• Attacks consist of tonic spasm, potentially involving the whole body but more commonly localized to the initiating limb or confined to one side.
• In three cases, the movements had a writhing character reminiscent of torsion spasm, with clonic movements being absent.
• A sensory aura, when present, began in the initiating limb and spread briefly before the spasm.
• The pattern of attack was generally stereotyped, though attacks might be arrested before fully developing.
• Consciousness was never lost, although transient clouding was sometimes evident.
• Attacks could sometimes be voluntarily induced if the provoking movement was abrupt and forceful.
• Kertesz (1967) introduced the term "paroxysmal kinesigenic choreoathetosis," emphasizing:
  • Provocation by movement.
  • Short duration of episodes.
  • Good response to phenytoin.
  • Familial occurrence, initially speculated to be recessive but later understood as autosomal dominant with reduced expressivity.

Genetic Findings

• Szepetowski et al. (1997) described four families where benign infantile convulsions were inherited as an autosomal dominant trait along with variably expressed "paroxysmal choreoathetosis."
• Eight patients had infantile convulsions followed by later development of choreoathetoid movements, with strong linkage evidence for the abnormal gene in the pericentromeric region of chromosome 16.
• It had long been believed that a channelopathy would be the cause of PKD (Berkovic, 2000).

• PKD and PRRT2 mutations
  • Chen et al. (2011) found that PKD was caused by changes in the gene for proline-rich transmembrane protein 2 (PRRT2), using exome sequencing and linkage analysis.
  • Ebrahimi-Fakhari et al. (2015) found 1,444 patients with 70 different PRRT2 mutations over a 4-year period.
    • Most cases were familial, with almost 80% carrying the c.649dupC frameshift mutation.
    • 95% of patients fell into the diagnostic spectrum of benign familial infantile convulsions, infantile convulsions followed by PKD, or PKD alone.
  • Silveira-Moriyama et al. (2013) described 11 patients with childhood-onset PRRT2-mutation-positive PKD:>
    • Six females and five males.
    • Mean age at onset: 8 years and 8 months (range: 5–11 years).
    • Duration of incidents: Always less than 1 minute, often less than 30 seconds.
    • Frequency: Multiple episodes per day (range 1–10) before medication.
    • Carbamazepine or phenytoin led to complete abolition of episodes in all treated patients.
    • Eight out of 11 patients reported occurrences at rest.
    • Some patients could prevent occurrences by performing particular movements when they felt the aura.
  • Clinical Observations
    • PKD episodes in PRRT2 mutation carriers were bilateral and always choreoathetoid.
    • Non-carriers experienced more dystonic episodes.
    • 45% of non-mutation carriers had episodes lasting less than 5 seconds, compared to only 12% of mutation-positive patients.
    • PRRT2-positive patients responded well to carbamazepine, with some experiencing cessation of episodes at doses as low as 50mg/day.
    • Non-carriers had a less impressive response to carbamazepine.

  • Other Manifestations of PRRT2 Mutations

    • Multiple phenotypes can appear in families with PKD, including other manifestations beyond movement disorders.
    • Separating the movement disorder from other PRRT2-related manifestations would be an artificial division.

Treatment and Medication

• Lishman et al. (1962) noted phenytoin as effective, while phenobarbitone gave variable results
• Carbamazepine is generally preferred over phenytoin for treating PKD in children.
• For patients at risk of Stevens-Johnson syndrome (HLAB*1502 positive), sodium valproate may be an effective alternative (Erro et al. 2014).
• Patients on carbamazepine may still experience auras but no subsequent episodes.
• If medication is missed, patients can have stronger episodes due to the lack of caution in sudden movements.
• Long-term follow-up studies of PKD patients are lacking, but some reports suggest subsidence of events in adult life, possibly due to a less vigorous lifestyle.

References

• Berkovic S (2000) Paroxysmal movement disorders and epilepsy. Links across the channel. Neurology 55: 169–70.
• Cheng W, Li X, Chen YY (2023) [The Biography and Achievements of Japanese Psychiatrist Syuzo Kure]. Zhonghua Yi Shi Za Zhi 53 (5):308-312. DOI: 10.3760/cma.j.cn112155-20230224-00017 PMID: 37935514.
• Chen WJ, Lin Y, Xiong ZQ, et al. (2011) Exome sequencing identifies truncating mutations in PRRT2 that cause paroxysmal kinesigenic dyskinesia. Nat Genet 43: 1252–5.
• Ebrahimi-Fakhari D, Saffari A, Westenberger A, Klein C (2015) The evolving spectrum of PRRT2-associated paroxysmal diseases. Brain 138: 3476–95
• Erro R, Sheerin UM, Bhatia KP (2014) Paroxysmal dyskinesias revisited: a review of 500 genetically proven cases and a new classification. Mov Disord 29: 1108–16.
• Jankovic J, Demirkiran M. Classification of paroxysmal dyskinesias and ataxias. Adv Neurol 2002;89:387–400.
• Kertesz A (1967) Paroxysmal kinesigenic choreoathetosis. Neurology 17: 680–90.
• Kure S. Atypical Thomsen’s disease. Tokyo Igakukai Zasshi (J Tokyo Med Assoc) 1892;6:505–514.
• Lishman WA, Symonds CP, Whitty CW, Willison RG (1962) Seizures induced by movement. Brain 85: 93–108
• Silveira-Moriyama L, Gardiner AR, Meyer E, et al. (2013) Clinical features of childhood-onset paroxysmal kinesigenic dyskinesia with PRRT2 gene mutations. Dev Med Child Neurol 55: 327–34.
• Szepetowski P, Rochette J, Berquin P, et al. (1997) Familial infantile convulsions and paroxysmal choreoathetosis: a new neurological syndrome linked to the pericentromeric region of human chromosome 16. Am J Hum Genet 61: 889–98.

Cite this: 

Cite this: CNKE contributors.Paroxysmal Kinesigenic Dyskinesias. CNKE.org, The Child Neurology Knowledge Environment. 29 December 2024. Available at: https://cnke.org/articles/271 Accessed  29 December 2024.