Episodic ataxia
Mutations of the gene KCNA1, which encodes the voltage-gated potassium channel KV1.1, are responsible for this subtype of episodic ataxia.
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.
It is assumed, though not yet proven, that decrease in KV1.1 mediated current leads to prolonged action potentials in interneurons and basket cells.
Patients with EA2 may also present with progressive cerebellar atrophy, nystagmus, vertigo, visual disturbances and dysarthria.
Attacks can be accompanied by increased heart rate and blood pressure, moderate to severe shaking, and stuttering.
Like EA1, attacks can be precipitated by exercise, emotional stress/agitation, physical stress, or heat (overheated body temperature) but also by coffee and alcohol.
CACNA1A is heavily expressed in Purkinje cells of the cerebellum where it is involved in coupling action potentials with neurotransmitter release.
The tottering mouse is a widely used model to study EA2, as it developed a spontaneous homologous mutation in Cacna1a in the early 1960s.
[20] Alternatively, some CACNA1A mutations, such as those seen in familial hemiplegic migraine type-1, result in increased Ca2+ entry and, thereby, aberrant transmitter release.
[citation needed] These patients can present with an overlapping phenotype of ataxia and seizures similar to juvenile myoclonic epilepsy.
As this subunit is expressed in the cerebellum, it is assumed that such increased current results in neuronal hyperexcitability Coding and noncoding variation of the human calcium-channel beta4-subunit gene CACNB4 in patients with idiopathic generalized epilepsy and episodic ataxia.
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.
After enrolling in school, he developed bouts of rhythmic arm jerking with concomitant confusion, also lasting approximately 30 minutes.
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.
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.
