Treatment of OPCA with Amantadine
Abstract & commentary
Source: Botez MI, et al. Amantadine hydrochloride treatment in olivopontocerebellar atrophy: A long-term follow-up study. Eur Neurol 1999;41:212-215.
Botez and colleagues have previously reported improved results using amantadine to treat late onset heredodegenerative spinocerebellar ataxia (SCA). The previous efforts by Boetz et al were either open or double-blinded (Botez MI, et al. Can J Neurol Sci 1991;18:307-311; Botez MI, et al. J Neurol Neurosurg Psychiatry 1996;61:259-264). Both studies showed favorable results in late-life ataxias, but not with Fried-reich’s ataxia. Also, however, neither trial lasted more than four months or more.
Botez et al now report an open study of outcomes from amantadine in 33 previously selected patients with SCA. Twenty-one proceeded with the trial and 12 refused treatment, apparently following the advice of other physicians. Treats and controls were relatively similar by gender, age, disease duration, and length of treatment. Apparently, no treated patient withdrew from the study.
Functional evaluations of all patients included tests of reaction time (RT) and movement time (MT) (in response to auditory or visual stimulation), using eight successive stimuli in each hand. Because of considerable geographical distances, patients were contacted monthly by telephone to determine compliance and any side effects. Initial personal examinations were followed by two direct revisits—one at a mean of 24 months and the second at 45 ± 4 months for the treated patients and ± 41 for the control patients. By the third visit, all 12 controls were symptomatically worse in both RT and MT testing. Those treated with amantadine improved in three out of four RT measurements by the 24th month visit and one of the four at the 45th week. Movement time was improved in three of four measurements on both the second (24 months) and 45th, third, final evaluation.
Botez et al indicate only the presence of mild weight loss as having affected any of the amantadine-treated group.
Commentary
This study reported meticulous care in choosing testing patients with adult-acquired SCA. Not well understood is that patients on amantadine improved their right-side bodily function more than the left. Overall quality-of-life function receives no comment, although Botez et al speculate that the effect of amantadine might be to activate cerebellar-midbrain dopaminergic pathways. Nevertheless, Botez et al cite experiments in which amantadine improves MT in mutant mice by acting as an NMDA antagonist. Whatever the mechanism, these potentially important observations deserve testing a larger cohort in a double-blind, more rigorous clinical program. Such testing must be accompanied by a broader number of quantitative motor tests, serial video-monitored changes in behavior, and reaction as to patients’ general improvement. As one of our colleagues, Dr. Steven Frucht of the Columbia-Presbyterian Movement Disorders Center, advises us, amantadine may sometimes benefit multisystem atrophy and mild cases of Parkinson’s disease. Could this be a factor in any of Botez’s patients? —fp
Amantadine has recently been tested for its action on spinal cerebellar atrophy (SCA). Which one of the following statements is correct?
a. Amantadine-receiving patients with SCA are improved in reaction time (RT) and movement time (MT) only at a 24-month therapeutic follow-up interval.
b. At the 24-month review, the SCA patients not taking amantadine are equally improved.
c. SCA patients taking amantadine improve in both RT and MT at 45 months.
d. Patients taking amantadine for 45 months are said to improve more in the right side of their bodies than the left.
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