Onset of EA1 occurs during early childhood to adolescence and persists throughout the patients life. Attacks last from seconds to minutes. Mutations of the gene KCNA1, which encodes the voltage-gated potassium channel KV1.1, are responsible for this subtype of episodic ataxia. KV1.1 is expressed heavily in basket cells and interneurons that form GABAergic synapses on Purkinje cells. The channels aid in the repolarization phase of action potentials, thus affecting inhibitory input into Purkinje cells and, thereby, all motor output from the cerebellum. EA1 is an example of a synaptopathy. There are currently 17 KV1.1 mutations associated with EA1, Table 1 and Figure 1. 15 of these mutations have been at least partly characterized in cell culture based electrophysiological assays wherein 14 of these 15 mutations have demonstrated drastic alterations in channel function. As described in Table 1, most of the known EA1 associated mutations result in a drastic decrease in the amount of current through KV1.1 channels. Furthermore, these channels tend to activate at more positive potentials and slower rates, demonstrated by positive shifts in their V½ values and slower τ activation time constants, respectively. Some of these mutations, moreover, produce channels that deactivate at faster rates (deactivation τ), which would also result in decreased current through these channels. While these biophysical changes in channel properties likely underlie some of the decrease in current observed in experiments, many mutations also seem to result in misfolded or otherwise mistrafficked channels, which is likely to be the major cause of dysfunction and disease pathogenesis.
He required "balance therapy" as a young child to aid in walking and has a number of ataxic attacks, each separated by months to years. These attacks were precipitated by fever. He has cerebellar atrophy and subclinical seizures. During later attacks, he also presented with distortions of the left hemifield, ataxia, slurred speech, followed by headache. After enrolling in school, he developed bouts of rhythmic arm jerking with concomitant confusion, also lasting approximately 30 minutes. He also has presented, at various times, with migraines. This patient carries a proline to arginine substitution in the fifth transmembrane-spanning segment of the gene SLC1A3. This gene encodes the excitatory amino acid transporter 1 (EAAT1) protein, which is responsible for glutamate uptake. In cell culture assays, this mutation results in drastically decreased glutamate uptake in a dominant-negative manner. This is likely due to decreased synthesis or protein stability. As this protein is expressed heavily in the brainstem and cerebellum, it is likely that this mutation results in excitotoxicity and/or hyperexcitability leading to ataxia and seizures. Mutations in EAAT1 (GLAST) have subsequently been identified in a family with episodic ataxia. Diagnosis
Treatment
Depending on subtype, many patients find that acetazolamide therapy is useful in preventing attacks. In some cases, persistent attacks result in tendon shortening, for which surgery is required. References
External links

GeneReviews/NCBI/NIH/UW entry on Episodic Ataxia Type 1, Episodic Ataxia with Myokymia, Hereditary Cerebellar Ataxia with Neuromyotonia
GeneReviews/NCBI/NIH/UW entry on Episodic ataxia type 2