Familial Paroxysmal Kinesigenic Ataxia and Continuous Myokymia

Abstract

A large family with paroxysmal ataxia and continuous myokymic discharges is described. The disorder is of autosomal dominant inheritance. During attacks coordination of movements and balance are disturbed; often a postural tremor of the head and the hands and fine twitching in some of the facial and hand muscles are present. The attacks usually last a few minutes and may occur several times per day. They first appear in childhood and tend to abate after early adulthood. The attacks are frequently precipitated by kinesigenic stimuli similar to those in paroxysmal kinesigenic choreoathetosis. Their occurrence can be reduced or prevented by carbonic anhydrase inhibitors. Between attacks a slight postural tremor and ataxia was found in a few of the elderly affected members. Fine rippling myokymia was obvious in a few and could be detected on close inspection in about half of the adults. Electromyography (EMG) showed myokymic discharges in all affected members. The characteristics and reactivity of this myokymic activity suggest multiple impulse generation in the peripheral nerves.

Episodic Ataxia Type 1: A Neuronal Potassium Channelopathy

“…Lubbers et al 40 studied the response of an EA-1 family to acetazolamide. All six members were affected by paresthesia (in accordance with reports from other families 10 ), and this caused the medication to be ACZ ϭ acetazolamide; EA-1 ϭ episodic ataxia type 1; N/A ϭ data not available.…”

“…To date, 11 individuals from four unrelated families have been reported to have epilepsy. 10,17,27,37 Van Dyke et al 27 described a female with generalized motor seizures and an abnormal EEG who had a partial response to phenytoin. Brunt and van Weerdan 10 in 1990 identified three members of an EA-1 family with 28 affected members who had abnormal EEGs.…”

Episodic Ataxia Type 2

“…It caused fewer side effects and was most effective in dosages between 50 and 300 mg daily. 62 Nevertheless, ACTZ is the drug of first choice, with sulthiame as an alternative treatment option. Recently, Scoggan et al 63 identified a new missense mutation in exon 12 of the CACNA1A gene from a patient with EA 2; the symptoms were controlled with a combination of ACTZ and valproic acid.…”

Episodic ataxia type 1 mutation F184C alters Zn2+-induced modulation of the human K+ channel Kv1.4-Kv1.1/Kvβ1.1

“…The disease is characterized by symptomatic attacks of imbalance and uncontrolled movements that may be triggered by physical or emotional stress (3,8,12,22,60). The duration of the attacks of ataxia varies: they may occur several times a day or once a year.…”

“…Although the symptoms vary between and within families, two symptoms are always observed: an ataxic gait during attacks and myokymia. The latter symptom is characterized by continuous muscle activity that can be detected as a rhythmic electromyography activity with a pattern of repeated duplets and multiplets (12,22). Genetic linkage studies have localized the EA1 locus to chromosome 12p13 (36).…”