Episodic ataxia

Episodic ataxias are characterized by intermittent symptoms or episodes that can vary in duration, lasting from minutes to days, consisting of slurred speech, a feeling of dizziness, ringing in the ears, abnormal posturing, unsteadiness and sometimes paralysis of one side of the body. Many patients with episodic ataxia complain of migraine headaches. Attacks can be as frequent as several times a week, but may occur much less frequently, once or twice a year. Precipitating causes for episodic ataxia attacks are unknown, though sometimes are attributed to ingestion of alcohol or caffeine, stress, fatigue, exposure to some paint thinners (toluene), and some medications such as phenytoin. The disease is usually autosomal dominant. Episodic ataxia may be caused by sequence changes in several different genes. The attacks may respond to medicines called acetazolamide (Diamox), topiramate (Topamax) or 4-aminopyridine (Ampyra).” There are many different types of episodic ataxia. Using a numbering system similar to the SCA disorders, episodic ataxias are labeled using the acronym “EA” and then numbered in the order of their discovery.

Episodic ataxias are often called “channelopathies.” Channels are proteins in our brain cells that provide a pathway for certain chemicals to move in and out of brain cells. This transmission of chemicals in and out of brain cells is an important part of how our brain sends signals.

EA1
This type of ataxia is caused by sequence changes in a gene called KCNA1. This gene encodes a channel for Potassium to move in and out of brain cells. The chemical abbreviation for potassium is “K” which accounts for the “K” in KCNA1. Symptoms often begin in childhood or teenage years. Episodes of ataxia may last from several seconds to several minutes. The episodes can rarely last for hours. Episodes may occur several times in a day, or only a few times per month. During the episodes, individuals experience ataxia (loss of balance and coordination), contractions and tightening of muscles, double vision, nausea, headache, and difficulty speaking or breathing. In between episodes, patients may experience “myokymia” which is a twitching or rippling of certain muscles. Genetic testing for EA1 is available in the United States.

EA2
This type of ataxia is caused by sequence changes in a gene called CACNA1A. This gene encodes a channel for calcium to move in and out of brain cells. The chemical abbreviation for calcium is “Ca” which explains the “Ca” in CACNA1A. The symptoms during the episodes are very similar to the episodes described above for EA1. One main difference is the episodes in EA2 may last much longer (sometimes lasting for days). In between episodes, individuals may have problems with eye movements and ataxia. Symptoms may grow worse and MRI sometimes shows the middle part of the cerebellum (the vermis) shrinking. Episodes may be triggered by stress, caffeine, alcohol, or exertion.

It is interesting to note that the CACNA1A gene is also involved in SCA6 and in a condition called familial hemiplegic migraine. About half of individuals with EA2 have migraines.

Genetic testing for EA2 is available in the United States as familial hemiplegic migraines gene.

EA3
EA3 has been described in some Canadian Mennonite families. During episodes, patients may experience vertigo (dizziness) and tinnitus (ringing in the ears). No gene has been identified for this condition.

EA4
This type of episodic ataxia has been described in 2 Caucasian families from North Carolina. No gene has yet been identified.

EA5
This type of episodic ataxia is caused by sequence changes in a gene called CACNB4. This gene encodes a channel that allows calcium to move in and out of nerve cells. This type of ataxia has been described in Caucasian families from Germany and Canada. This same gene is also involved in some types of epilepsy. Genetic testing for EA5 is only available in Europe.

EA6
EA6 is caused by sequence changes in a gene called SLC1A3. This gene encodes a channel that allows chemicals called “amino acids” in and out of brain cells. This type of episodic ataxia has only been described in a handful of families. Genetic testing is available only in Europe.

EA7
EA7 is the most recently described form of episodic ataxia. Symptoms generally begin before adulthood and episodes can last from hours to days in length. Attacks were infrequent (monthly to yearly) and may decrease in frequency with age. No gene testing is available.