Increased CSF ratio of glutamine to branched chain amino acids in DOPA non responsive but gabapentin responsive dystonia

Abstract

Dystonia is a common neurological disorder, but its pathophysiological basis is poorly understood. Primarily dystonic movement disorders seem to be related to basal ganglia and the biogenic amine system of neurotransmission. Pharmacological therapy is governed by personal experience, often resulting in drug cocktails. The use of gabapentin has been sporadically reported for the treatment of dystonia. Patients: We report on two patients with severe Levodopa non-responsive torsion dystonia as a symptom of an underlying neurodegenerative disorder. Both patients demonstrated impressive improvement on gabapentin treatment with a decrease in dystonia attacks from hundreds per day to remission. The CSF amino acid pattern of both patients revealed an increased concentration of glutamine and decreased concentrations of branched chain amino acids (BCAA). Discussion: These results may indicate an increased central nervous system glutamine/glutamate synthesis at the expense of BCAA via the major synthesizing pathway, the astrocytal branched chain aminotransferase, an enzyme which is inhibited by gabapentin. While both patients had a drug history including GABAergic substances like vigabatrin and baclofen with no effect on the dystonia, we suggest that gabapentin is effective by decreasing glutamate/glutamine synthesis. This is supported by the normalization of glutamine and BCAA in CSF during gabapentin treatment. Based on these observations, we conclude that analysis of CSF glutamine and BCAA may be useful in monitoring gabapentin treatment in patients with dystonia.