Article Figures & Data
Figures
- Fig. 1.
Effects of enhanced monoaminergic transmission on dystonia induced by cerebellar microinjection of kainate. (A) Peripheral administration of amphetamine, which nonselectively increases the extracellular concentrations of the monoamines dopamine, norepinephrine, and serotonin, dose-dependently reduced the severity of dystonia induced by microinjection of kainate to the cerebellum (one-way ANOVA; F3,28 = 4.813, P < 0.01, n = 8/dose). (B) The selective norepinephrine reuptake inhibitor nisoxetine did not affect the disability score (one-way ANOVA; F3,27 = 0.468, NS, n = 7 to 8/dose). (C) Citalopram, a selective serotonin reuptake inhibitor, did not affect the disability score (one-way ANOVA; F3,26 = 0.317, NS, n = 7 to 8/dose). (D) The selective dopamine reuptake inhibitor GBR-12909 dose-dependently reduced the severity of dystonia (one-way ANOVA; F3,28 = 3.853, P < 0.05, n = 8/dose). Disability scores lower than 10 (dashed lines) suggest abnormal motor behavior, such as an unsteady gait, but not overt dystonia. Values represent the mean of the cumulative disability score in 1 hour ± S.E.M. *P < 0.05; **P < 0.01 compared with vehicle, Holm-Sidak multiple comparisons test. NS, not statistically significant.
- Fig. 2.
Effects of dopamine receptor agonists on dystonia induced by cerebellar microinjection of kainate. (A) The nonselective dopamine receptor agonist apomorphine dose-dependently reduced the severity of dystonia (one-way ANOVA; F3,29 = 3.259, P < 0.05, n = 8–10/dose). (B) The D1 dopamine receptor selective agonist SKF-81297 did not affect the severity of cerebellar kainic acid-induced dystonia (one-way ANOVA; F3,29 = 0.325, NS, n = 7–10/dose). (C) The D2 dopamine receptor selective agonist quinpirole significantly reduced the severity of dystonia (one-way ANOVA; F3,30 = 7.233, P < 0.001, n = 8 to 9/dose). Disability scores lower than 10 (dashed lines) suggest abnormal motor behavior, such as an unsteady gait, but not overt dystonia. Values represent the mean of the cumulative disability score in 1 hour ± S.E.M. *P < 0.05; **P < 0.01 compared with vehicle, Holm-Sidak multiple comparisons test.
- Fig. 3.
Synergistic effects of D1 plus D2 dopamine receptor activation on the severity of cerebellar mediated dystonia. Administration of a low dose of quinpirole (0.5 mg/kg) did not affect the severity of dystonia compared with vehicle administration (two-tailed Student’s t test, t = 0.629). However, administration of quinpirole plus SKF-81297 significantly reduced the severity of dystonia induced by cerebellar microinjection of kainate (one-way ANOVA; F3,30 = 4.841, P < 0.01, n = 7–11/dose). Disability scores lower than 10 (dashed lines) suggest abnormal motor behavior, such as an unsteady gait, but not overt dystonia. Values represent the mean of the cumulative disability score in 1 hour ± S.E.M.; *P < 0.05 compared with quinpirole alone, Holm-Sidak multiple comparisons test.
- Fig. 4.
Regional analysis of the effects of apomorphine on dystonia induced by cerebellar microinjection of kainate. Microinjection of apomorphine into the striatum significantly reduced the severity of the dystonia (Student’s t test, one-tailed, P < 0.05 compared with saline), whereas cerebellar microinjection of apomorphine did not affect the severity of dystonia (Student’s t test, one-tailed, NS compared with saline). Disability scores lower than 10 (dashed lines) suggest abnormal motor behavior, such as an unsteady gait, but not overt dystonia. Values represent the mean of the cumulative disability score in 1 hour ± S.E.M.; *P < 0.05 compared with microinjection of vehicle in the same brain region.
Tables
- TABLE 1
Patient studies examining the efficacy of dopaminergic drugs for the treatment of dystonias
Drug Type of Dystonia Patients Improved/Patients Testeda Type of Study Level of Evidenceb Year Reference Amphetamine Cervical, multifocal (cervical and foot) 2/2 Case reports IV 1942 Myerson and Loman (1942) Cervical 1/1 Case report IV 1943 Patterson and Little (1943) Apomorphine Cervical 2/7 Double-blind, placebo crossover and open-label IV 1978 Tolosa (1978) Cervical 3/3 Double-blind, placebo crossover III 1982 Frattola et al. (1982) Craniofacialc 5/5 Single-blind, placebo crossover IV 1979 Tolosa and Lai (1979) Craniofacial 2/2 Case reports IV 1982 Micheli et al. (1982) Craniofacial 12/23 Single-blind, placebo crossover IV 1986 Micheli and Fernandez Pardal (1986) Generalized 2/2 Case reports IV 1973 Braham and Sarova-Pinhas (1973) Generalized 1/1 Case report IV 1996 Zuddas et al. (1996) Segmental (cervical, spasmodic dysphonia, and craniofacial) 1/1 Case report IV 1993 Vidailhet et al. (1993) Bromocriptine Cervical 0/8 Single-blind, placebo crossover IV 1976 Lees et al. (1976) Cervical 0/14 Randomized, double-blind, placebo crossover III 1979 Juntunen et al. (1979) Craniofacial 0/2 Case reports IV 1982 Micheli et al. (1982) Generalized, craniofacial plus cervical 2/3 Double-blind, placebo crossover IV 1981 Stahl and Berger (1981) Generalized, cervical, craniofacial 5/8 Double-blind, placebo crossover IV 1982 Stahl and Berger (1982) Generalized, segmental (cervical/limb), truncal, cervical 2/13 Blinded raters, no placebo IV 1982 Girotti et al. (1982) Generalized, unspecified focal 2/10 Open-label followed by double-blind study in the two responders IV 1984 Obeso and Luquin (1984) Generalized, hemidystonia, cervical, segmental (oromandibular and laryngeal), multifocal (cervical and foot) blepharospasm 7/13 Randomized, double-blind, placebo crossover III 1985 Newman et al. (1985) Lisuride Cervical 3/3 Double-blind, placebo crossover III 1982 Frattola et al. (1982) Craniofacial 2/2 Case reports IV 1982 Micheli et al. (1982) Craniofacial 1/7 Open label IV 1983 Marsden et al. (1983) Craniofacial 13/23 Single-blind, placebo crossover IV 1986 Micheli and Fernandez Pardal (1986) Craniofacial 1/1 Case report IV 1988 Micheli et al. (1988) Craniofacial 1/9 Randomized, double-blind, placebo crossover II 1988 Bassi et al. (1982) Generalized, cervical 6/7 Double-blind, placebo crossover III 1982 Ransmayr et al. (1988) Generalized, unspecified focal 0/10 Open-label IV 1984 Obeso and Luquin (1984) Generalized, segmental (unspecified regions), hand, cervical, craniofacial, myoclonic, Parkinsonism with dystonia, tardive, unspecified 8/42 Open-label followed by randomized, double-blind, placebo crossover for the eight patients who improved IV 1985 Quinn et al. (1985) Generalized, cervical, craniofacial 6/9 Double-blind, placebo crossover IV 1985 Nutt et al. (1985) ↵a The definition of “improved” varied across publications and is summarized here exactly as reported.
↵b Based on the updated scheme for “Classification of Evidence for Therapeutic Studies” established by the American Academy of Neurology in 2015.
↵c Craniofacial is used synonymously with Meige syndrome or orofacial dystonia.
