Treatment of Ataxia in Cortical Cerebellar Atrophy with the GABAergic Drug Gabapentin

Abstract

The aim of this work was to investigate the efficacy of the GABAergic drug gabapentin in the treatment of the cerebellar signs caused by cortical cerebellar atrophy (CCA). Ten patients with CCA received gabapentin in single doses of 400 mg in an open-label study; thereafter, daily administration of 900–1,600 mg of gabapentin was continued during at least 4 weeks. An ataxia scale based on clinical findings was used to evaluate the cerebellar signs at baseline and after administration of the drug. A statistically significant improvement of the ataxia scores was found after single doses of 400 mg of gabapentin and after the administration of 900–1,600 mg of this drug during 4 weeks, as compared to the results obtained at baseline. An important clinical amelioration was also evident. Gabapentin has been demonstrated to be capable of improving the cerebellar signs in cases of CCA, after single doses and after continued administration of the drug during 4 weeks. GABAergic enhancement or supplementation could play an important role in the treatment of diseases of the cerebellar cortex associated with a deficit of GABA.

Spinocerebellar ataxia type 6 (SCA6): Clinical pilot trial with gabapentin

“…The study protocol was basically the same as previously reported by Gazulla et al [19], with slight modifications. The patients except patient 11 were admitted at least 5 days around the initiation of gabapentin administration.…”

“…These drugs have been reported to improve ataxia in cases of cortical cerebellar ataxia (CCA) [19,20]. As there is a similarity of the neuropathological findings between SCA 6 and CCA, and that gabapentin may be able to decrease the inactivation of P/Q-type VDCCs, it is postulated that gabapentin could be effective in the treatment of cerebellar ataxia in SCA6 patients [16,17].…”

“…Serum gabapentin concentration was likely to be associated with renal function. Gazulla et al used gabapentin in CCA patients in daily doses ranging from 900 to1,600 mg [19]. For the maximum clinical effects on SCA6 patients, the total daily doses of gabapentin may need to be carefully adjusted in each patient.…”

Neurochemistry and Neuropharmacology of the Cerebellar Ataxias

“…Ten patients were initially given a single dose of 400 mg of gabapentin, followed by doses between 900 and 1600 mg per day during four weeks. Every patient experienced an improvement in ataxia, and in three, gait became normal (25). Gabapentin interacts with the 2- subunit of the P/Q type voltage-dependent calcium channels (VDCC) (26), stimulates GABAergic neurotransmission by presynaptic mechanisms (27) and increases the concentration of GABA in the brain of healthy adults (28).…”

Spinocerebellar degeneration

“…Baclofen, a GABA-B agonist, also tends to increase ataxia. Gabapentin has been reported in an open trial to improve cerebellar signs in ten patients with cerebellar cortical atrophy [20]. Thyrotropin-releasing hormone (TRH) may also modulate GABA receptors and has shown mild efficacy in Class 1 trials [21].…”