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We read with interest the article by Miyagiet al 1 and comment on the medical treatment of toluene induced tremor. Microdialysis experiments in rats have shown that inhalation of toluene increases extracellular γ-aminobutyric acid (GABA) concentrations within the cerebellar cortex2 which probably explains why GABA agonists including benzodiazepines (for example, clonazepam) are not very effective in toluene induced tremor and ataxia. Rat experiments also showed a 50% reduction in brain catecholaminergic neurons.3 Degeneration of certain cerebellar pathways is probably responsible for the loss of this dopaminergic innervation.4 Dopamine agonists could therefore be of potential interest in the treatment of toluene induced tremor. This hypothesis was explored in a recently described case,5 which showed remarkable clinical and iconographic similarities with that described by Miyagi et al 1: (a) long history of chronic toluene inhalation, (b) marked postural tremor, (c) progressive worsening of the symptoms despite abstinence from inhalant misuse, and (d) mild cerebral atrophy and marked low signal intensity in globus pallidi, thalami, red nuclei, and substantia nigrae on T2 weighted MRI. As our patient's tremor was progressive, medical treatment with a dopamine agonist was considered. One particular agent (amantadine) caught our attention because it had proved successful in the treatment of postural tremor and ataxias of heredodegenerative disorders in which the dentatorubro-olivary system is affected. In addition, there is evidence that catecholaminergic pathways are also involved in this type of ataxias, supported by low concentrations of these neurotransmitters in the CSF of patients with heredodegenerative ataxias.6 In our patient, amantadine hydrochloride (100 mg twice daily) abolished postural tremor and ataxia completely over a 3 month period.
Subsequently, the treatment was discontinued, which resulted in relapse of the tremor and ataxia. He was rechallenged to amantadine, which progressively offered him the same clinical improvement as in the first 3 months. After 3 years the treatment was discontinued without any sign of relapse.
Although this finding needs confirmation, amantadine treatment could form a new approach in the medical treatment for toluene induced tremor and ataxia. Intractable cases would then justify a more aggressive approach such as ventrointermedius thalamotomy.
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