Improvement of ataxia in cortical cerebellar atrophy with the drug gabapentin.

To the Editor: Cortical cerebellar atrophy (CCA) has been found to be associated with a predominant loss of Purkinje cells in the anterior vermis, and a selective tissular decrease in the content of the neurotransmitter gamma-amino-butyric acid (GABA), causing a pure cerebellar syndrome. Drugs enhancing GABAergic action in the central nervous system have not been tried previously in the treatment of this disease, although gabapentin was found capable of improving cerebellar signs related to atrophy of the cerebellar cortex in a case of adult GM2 Gangliosidosis. Gabapentin is a GABA molecule with an attached cyclohexane ring. It binds to the 2subunit of the voltage-dependent P/Q calcium channel, and increases brain GABA concentration either after single doses or continuous administration during several weeks. Peak serum concentration (Tmax) of gabapentin occurs 2 to 3 hours after ingestion, and its half-life (T1/2) is between 5 and 7 hours. The objective of this work has been to investigate the efficacy of the GABAergic drug gabapentin in the treatment of the cerebellar signs caused by CCA. Ten patients with CCA received gabapentin in single doses of 400 mg in 3 occasions on alternate days; thereafter, daily administration of 900 to 1600 mg of gabapentin was continued during at least 4 weeks. The ataxia assessment was performed under baseline conditions (without taking any drug with action on the central nervous system), and 3 hours after oral administration of single doses of 400 mg of gabapentin (Tmax of the drug), on 3 occasions on different days. The ataxia assessment was performed again after 4 weeks of continued treatment with gabapentin in total daily doses ranging from 900 to 1600 mg. An ataxia scale based on the International Cooperative Ataxia Rating Scale (ICARS), that included items to evaluate spread of feet (0–4 points), walking capacities (0–8 p), knee-tibia test (0–4 p), finger-to-nose test (0–4 p), giving a maximal total ataxia scale (TAS) of 20 points, was used to evaluate the cerebellar signs at baseline and after administration of the drug. As this was considered a pilot investigation, the authors selected these items from ICARS because they were judged sufficient to assess the ataxic signs in CCA without resorting to use of the complete scale. Intermalleolar distance in centimeters was also measured. The study was approved by Hospital San Jorge’s ethics committee; informed consent was obtained from every patient. Statistical comparison of the scores obtained at each of the three baseline measurements, and of those obtained after each of the single doses of gabapentin, was performed using the Friedman test. The Wilcoxon paired t test was performed to compare the results obtained after the administration of single doses of gabapentin and those after prolonged administration with those at baseline conditions. Every patient was found to improve at assessment of ataxia taking the drug (Table 1). Three of them exhibited normal gait after 4 weeks of treatment. Symptoms of intolerance severe enough to interrupt prolonged administration of gabapentin were not experienced by any patient. Statistical analysis (using the Friedman test) did not show any significant difference between the three baseline scores, nor between the scores obtained after single doses of gabapentin, thereby dismissing any learning effect from the tests, or the accumulation of separate doses of the drug, at assessment. The results of the first baseline measurement, together with those obtained after the first single dose of gabapentin, were used for statistical comparison. Using the Wilcoxon paired t test, a statistically significant improvement of every ataxia item (P < 0.05) was found when comparing the scores recorded after single-dose administration of gabapentin with those at baseline. A statistically significant improvement was also found for each of the ataxia items when comparing the results obtained after prolonged administration of gabapentin with those at baseline. An improvement of each of the ataxia scores was found after prolonged administration of gabapentin, although only TAS reached statistical significance (P = 0.04), after comparison with the results obtained after single doses of the drug. The results of this study show that the administration of the drug gabapentin in single doses of 400 mg, as Clinical Neuropharmacology Vol. 26, No. 5, pp. 225–226 © 2003 Lippincott Williams & Wilkins, Inc., Philadelphia