Abstract
Background The potassium channel blocker 4-aminopyridine (4-AP) has long been used as symptomatic therapy for multiple sclerosis (MS) to treat spasticity and improve ambulatory speed, though evidence remains lacking. 4-AP selectively blocks fast voltage-gated potassium channels and increases calcium influx at nerve terminals, enhancing neuromuscular transmission. 4-AP is also used in animal models of epileptogenicity via this mechanism, and its therapeutic use or overdose in MS has been associated with several cases of new-onset seizures, which is otherwise a rare symptom in MS.
Cases Case one was a 66 year old woman with primary progressive MS presenting with two days of impaired gait and hyperkinetic movements leading to convulsive status epileptics (CSE). Case two was a 53 year old man with relapsing-remitting MS presenting just two days later with a day of hyperkinetic movements and agitation leading to CSE. Both cases were taking 4-AP from the same compounding pharmacy, having recently been dispensed the same batch, and both required intravenous sedation and intubation in an Intensive Care Unit. In neither case was an alternative pathology identified to account for new-onset CSE, but both patients subsequently made a good recovery and remained seizure free.
Conclusions We systematically reviewed similar reported cases (16 in total) of seizures associated with 4-AP, and found at least half were attributable to either intentional or unintentional overdose or drug compounding error. The majority developed status epilepticus requiring intravenous sedation and intubation, yet nearly all made complete recoveries and remained seizure free after cessation of 4-AP.
