Amantadine hydrochloride (AH) was administered (200 mg/day) for more than three months to 17 patients with Friedreich's ataxia (FA) and to 12 patients with olivopontocerebellar atrophies (OPCA) in an open clinical trial. Reaction time (RT) and movement time (MT) with the right and left hand were measured before and after treatment. A striking improvement on both RT and MT was observed in the OPCA group (on seven out of eight measures), whereas in the FA patients improvement was seen only in two out of four MT measures with no improvement in RT. Both groups had low levels of homovanillic acid (HVA) in their cerebrospinal fluid before treatment, relative to their controls. However, improvement with AH was not related to HVA levels. Can. J. Neurol. Sci. 1991; 18:307-311 Anatomical and behavioral neurochemical work on degenerative disorders has led to therapies which replace or potentiate the function of those neurotransmitters whose neurons have degenerated. This approach has triumphed mainly in Parkinson's disease, but it has not been of any use in Alzheimer's disease.In a preliminary study, we found low levels of the dopamine metabolite, homovanillic acid (HVA), in the cerebrospinal fluid (CSF) of patients with both Friedreich's ataxia (FA) and olivopontocerebellar atrophies (OCPA).1 2 Because amantadine hydrochloride (AH) is known to stimulate dopamine release, 3 this finding prompted us to test AH in FA and OPCA. An improvement in reaction time (RT) and movement time (MT) was seen in three FA and two OPCA patients. In an independent study, Petersen et al. 4 reported a beneficial effect of AH in FA patients in an open clinical trial.The aim of the present open clinical trial was two-fold: 1) to evaluate the therapeutic effect of AH separately in FA and OPCA patients using RT and MT measures; and 2) to determine whether the beneficial effects of AH are related to CSF HVA levels.
PatientsA neurological examination was performed independently by two neurologists (M.I.B. and O.L.P.). In addition to the routine neurological examination, in order to rule out mild parkinsonian rigidity, we also looked for signs of latent muscular parkinsonian rigidity as described by Noica and Draganesco. 5 With the patient in a relaxed recumbent position, the examiner holds the patient's forearm upright; he then elicits complete and continuous passive flexion and extension of the wrist. After 10-12 sec, the subject is asked to perform a voluntary slow movement with another limb, as, for example, raising a lower limb in the air. During such a manoeuvre, increasing local tonus gradually inhibits passive wrist movements. This increased resistance disappears after the patient returns to the initial relaxed state. In our experience, it is the most sensitive and pathognomonic clinical sign of early parkinsonian rigidity. 6 X-ray-computed tomographic (CT) scans were taken of all patients with an Elscint apparatus. 7 Those showing central (i.e. ventricular dilation) and cortical (i.e. cortical sulci dilation) atrophies according...