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Gabapentin Relieves Vertigo of Periodic Vestibulocerebellar Ataxia: 3 Cases and Possible Mechanism

In their article, Coin and Vance describe improvement of optokinetic-triggered vertigo (OKTV) in periodic vestibulocerebellar ataxia type 4, with small doses of gabapentin. They describe a switchlike effect of gabapentin on OKTV: one patient experienced improved vertigo 4 hours after single doses of 200 mg of gabapentin, with relief wearing off after 8 to 12 hours; interestingly, the patient also felt that gabapentin administration ameliorated ataxia. Gabapentin binds to the α2-δ subunit of the voltagedependent P/Q calcium channel and has been shown to stimulate expression of δGABAA receptors, to increase inhibitory tone in mouse cerebellum, and to increase brain γ-aminobutyric acid (GABA) concentration in healthy volunteers. Peak serum concentration (Tmax) of gabapentin occurs 2 to 3 hours after ingestion, its half-life (t1/2) being between 5 and 7 hours. GABA is the most important inhibitory neurotransmitter in the central nervous system. In the cerebellum, it is used by Purkinje cells to provide inhibitory outflow to the cerebellar nuclei. GABA content in the dentate nuclei of the cerebellum and cerebrospinal fluid has been found to be markedly and selectively reduced in late cortical cerebellar atrophy. In a previous study, 10 patients with cortical cerebellar atrophy were examined at baseline conditions and 3 hours after single doses of 400 mg of gabapentin. Intermalleolar distance (in centimeters) and the International Cooperative Ataxia Rating Scale items “walking capacities,” “spread of feet,” “knee-tibia test,” and “finger-to-nose test” were assessed: a clinical and statistically significant improvement was found in every item, when comparing the scores recorded after three single-dose administrations of gabapentin with those at baseline; the clinical benefit weaned off after several hours. Thus, gabapentin’s switchlike effect on cerebellar ataxia was demonstrated here. The improvement in cerebellar signs found 3 hours after single doses of gabapentin was coherent with the drug’s Tmax, and a simple test intended to single out symptoms that might benefit from gabapentin could be based on administration of single doses of this drug, with a favorable response predicting prolonged amelioration, as also found by Coin and Vance. In other studies, gabapentin improved ataxia in GM2gangliosidosis; spinocerebellar ataxia types 1, 2, and 6; and oscillopsia and ataxia in olivopontocerebellar atrophy. In other disorders with a deficiency in GABA content, such as progressive encephalomyelitis with rigidity, muscular spasms were suppressed by a combination of gabapentin and tiagabine, and in diaphragmatic myoclonus, gabapentin and tiagabine obtained symptomatic control. On the contrary, gabapentin was not effective in cervical dystonia, amyotrophic lateral sclerosis, Parkinson’s disease, progressive supranuclear palsy, and ataxia secondary to multiple sclerosis, presumably because a deficiency in GABA is not an essential neurochemical abnormality in these diseases. In consequence, considering its efficacy and tolerability, gabapentin should receive attention as a potential therapeutic agent for cerebellar ataxias and other motor disorders related to deficient GABA activity in the central nervous system, in which administration of single doses of this drug could predict prolonged clinical improvement.