A concise study of acetazolamide in Glut1 deficiency (G1D) epilepsy.

Epilepsy constitutes the most common paroxysmal manifestation of glucose transporter type 1 deficiency (G1D) and is generally considered medication-refractory. It can also prove therapeutic diet-resistant. We examined acetazolamide effects in G1D motivated by several longstanding and recent observations: First, the electrographic spike-waves characteristic of absence seizures often resemble those of G1D and, since the 1940s, they have occasionally been successfully treated with acetazolamide, well before G1D was segregated from absence epilepsy as a distinct syndrome. Second, synaptic inhibitory neuron failure characterizes G1D and, in other experimental models, this can be ameliorated by drugs that modify cellular chloride gradient such as acetazolamide. Third, acetazolamide potently stimulates model cell glucose transport in vitro. Seventeen antiepileptic drug or therapeutic diet-refractory individuals with G1D treated with acetazolamide were thus identified via medical record review complemented by worldwide individual survey. Acetazolamide was tolerable and decreased seizures in 76% of them, with 58% of all persons studied experiencing seizure reductions by more than one half, including those who first manifested myoclonic-astatic epilepsy or infantile spams. 88% of individuals with G1D continued taking acetazolamide for over 6 months, indicating sustained tolerability and efficacy. The results provide a novel avenue for the treatment and mechanistic investigation of G1D.