trimethoprim--sulfamethoxazole-drug-combination and Machado-Joseph-Disease

To evaluate the efficiency of a combination of trimethoprim and sulfamethoxazole in patients with spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD).. Placebo-controlled, double-blind crossover trial in 22 patients with genetically confirmed SCA3/MJD. Study phases of 6 months were separated by a washout period of 4 weeks. Dosages were a combination of trimethoprim, 160 mg, and sulfamethoxazole, 800 mg, twice daily for 2 weeks, followed by a combination of trimethoprim, 80 mg, and sulfamethoxazole, 400 mg, twice daily for 5.5 months.. Outpatient department of the Neurological Clinic, Ruhr-University, Bochum, Germany.. Ataxia ranking scale, self-assessment score, static posturography, and results of motor performance testing. Effects on the visual system were studied using the achromatic Vision Contrast Test System and the Farnsworth-Munsell 100-hue test for color discrimination. Physical and mental health were documented using the Medical Outcomes Study 36-Item Short-Form Health Survey. Subgroup analyses assessed the influence of age, sex, age at onset, duration of the disease, phenotype, and CAG repeat length on test performance.. Twenty of 22 patients completed the study. Dropouts were due to a rash (placebo phase) and an attempted suicide in a family conflict. Trimethoprim-sulfamethoxazole therapy had no significant effect in SCA3/MJD patients in the short-term analysis (2 weeks) or in the long-term interval (6 months).. In contrast to previous reports that studied smaller groups of patients, treatment with trimethoprim-sulfamethoxazole did not improve the diverse and complex movement disorders caused by SCA3/MJD. Trimethoprim-sulfamethoxazole had no effect on the visual system and cannot be recommended as a continuous treatment for SCA3/MJD patients.

Topics: Adult; Anti-Infective Agents; Cross-Over Studies; Double-Blind Method; Female; Humans; Machado-Joseph Disease; Male; Middle Aged; Posture; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Vision Tests

In 1988, Mello and Abbott incidentally found an effectiveness of sulfamethoxazole-trimethoprim (S-T), an antimicrobial combination which was prescribed for the treatment of dysuria, on neurologic dysfunction in a patient with MJD. However, the mechanism by which S-T exerts its pharmacological actions on the central nervous system was not delineated. The purposes of the present studies are to investigate whether or not S-T is effective in alleviating the neurological symptoms and signs in MJD, and then to clarify the mechanism how S-T exerts its pharmacological actions on the neurological deficits, and finally to test the effectiveness of tetrahydrobiopterin (BH4) as a treatment. (1) Sulfamethoxazole-trimethoprim double-blind, placebo-controlled, crossover trial. The clinical results were as follows; mild improvements of hyperreflexia of knee jerks and of rigospasticity of the legs during S-T treatment period. In addition, S-T significantly reduced the times of 8 motor activities on the timed tests. The biochemical results showed that basal levels of all biopterins and homovanillic acid in the cerebrospinal fluid(CSF) were reduced to less than half the levels of controls with other neurological diseases. After S-T treatment, total and oxidized form of biopterins in the CSF increased significantly. Therefore, S-T may be effective to neurologic deficits through its mechanism of increasing the level of brain biopterins in MJD. The present study prompted us to investigate whether or not tetrahydrobiopterin (BH4) is useful as a therapeutic strategy. (2) Tetrahydrobiopterin double-blind, placebo-controlled, crossover trial. The results were as follows: 1. Questionnaire. Choking was mildly improved on the first tetrahydrobiopterin (BH4) treatment day, though not significant (p < 0.10). 2. Neurologic examinations. Hyperreflexia of the knee jerks was mildly improved on the 10th day of BH4 treatment, but it was not significant (p < 0.10). 3. Timed tests. Significant improvements were seen on several timed tests. These results, though preliminary, implied that BH4 showed mild improvements of neurologic deficits.

Topics: Anti-Infective Agents; Biopterins; Double-Blind Method; Humans; Machado-Joseph Disease; Trimethoprim, Sulfamethoxazole Drug Combination

We performed a double-blind, placebo-controlled, crossover trial of sulfamethoxazole-trimethoprim (S-T) in 8 patients with Machado-Joseph disease (MJD), and measured the blood and cerebrospinal fluid levels of biopterins, biogenic amines or metabolites, and folate. The clinical results were as follows; mild improvements of hyperreflexia of knee jerks and of rigospasticity of the legs during S-T treatment period. In addition, S-T significantly reduced the times of 8 motor activities on the timed tests. The biochemical results showed that basal levels of all biopterins and homovanillic acid in the cerebrospinal fluid (CSF) were reduced to less than half the levels of those of controls with other neurological diseases. After S-T treatment, total and oxidized form of biopterins in the CSF increased significantly. Therefore, S-T may be effective to neurologic deficits through its mechanism of increasing the level of brain biopterins.

Topics: Adult; Biopterins; Double-Blind Method; Humans; Machado-Joseph Disease; Male; Middle Aged; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

A double-blind, placebo controlled, cross-over trial of sulfamethoxazole and trimethoprim was performed in a 62-year-old male patient who suffered from Machado-Joseph disease for 25 years. The patient, with cerebellar ataxia, akinetic-rigid syndrome and motor weakness but without any pyramidal features, had been chair-bound for 3 years before the trial. Bactrim therapy markedly improved performance on a physical examination which tested standing and gait, as compared to placebo session. Walker-assisted gait was possible again. For the first time, evaluation of spatio-temporal contrast sensitivity was performed and also revealed an improvement after Bactrim therapy as compared to placebo. These results suggest that Bactrim may be effective in degenerative neurological diseases and that Bactrim may have an overall effect on neurotransmission rather than solely possessing antispastic properties.

Topics: Analysis of Variance; Contrast Sensitivity; Double-Blind Method; Drug Combinations; Gait; Humans; Machado-Joseph Disease; Male; Middle Aged; Placebos; Sulfamethoxazole; Synaptic Transmission; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Desensitization, Immunologic; Drug Hypersensitivity; Humans; Machado-Joseph Disease; Male; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Antioxidants; Biopterins; Humans; Machado-Joseph Disease; Neurologic Examination; Trimethoprim, Sulfamethoxazole Drug Combination