Table 1. Trials and case series with aminopyridines in cerebellar disorders.
| Study | Study population | Drug | Daily dose | Trial design | Study period | No. of patients | Outcome |
|---|---|---|---|---|---|---|---|
| Struppetal. [11] | EA 2 | 4-AP | 5 mg rid | Case series | – | 3 | Prevention of attacks |
| Alleviation of ataxic symptoms | |||||||
| Strupp et al. [2] | EA 2 | 4-AP | 5 mg rid | Placebo-controlled | 8–12 weeks | 10 | Reduction of frequency and duration of attacks |
| Improvement in quality of life (VDADL score) | |||||||
| Claassen et al. [14] | EA 2 | 4-AP-SR | 10 mgbid | Observational | 2 weeks | 10 | Decrease of slow phase velocity (DBN) |
| Improvement of visual acuity | |||||||
| NCT01543750 | EA 2 | 4-AP-SR | 10 mg bid | Placebo-controlled | 8 weeks | – | Ongoing |
| EAT-2-TREAT | EA 2 | 4-AP-SR vs. acetazolamide | 10 mg bid | Placebo-controlled | 12 weeks | – | Ongoing |
| Strupp et al. [1] | DBN (different etiology) | 3,4-DAP | 20 mg | Placebo-controlled | Single dose | 17 | Reduction of slow phase velocity |
| Improvement of DBN (oscillopsia, postural stability) | |||||||
| Tsunemi et al. [19] | Pure cerebellar degeneration | 3,4-DAP | 20 mg bid | Controlled | 1 week | 15 | 3,4-DAP effective on DBN and oscillopsia |
| No effect on other ataxic symptoms | |||||||
| Kalla et al. [148] | DBN | 4-AP | 10 mg | Case report | Single dose | 1 | Improvement of DBN, smooth pursuit, VOR gain |
| Kallaetal. [18] | DBN | 4-AP | 10 mg | Controlled | Single dose | 15 | Improvement of slow-phase velocity (DBN) |
| Kalla et al. [20] | DBN | 3,4-DAP | 10 mg 3,4-DAP vs. 10 mg 4-AP | Placebo-controlled | Single dose | 8 | Reduction of slow phase velocity (DBN) |
| 4-AP | 4-AP showed more pronounced effect than equivalent doses of 3,4-DAP | ||||||
| Claassen et al. [22] | DBN | 4-AP | 5 mg qid vs. 10 mg qid | Placebo-controlled | 3 days 20 mg/day vs. 4 days 40 mg/day vs. 4 days placebo | 27 | Reduction of slow phase velocity (DBN), improvement of visual acuity, postural sway, and locomotor parameters |
| Schniepp et al. [26] | CACNA1A mutation | 4-AP | 5 mg rid | Case series | – | 2 | Improvement of gait |
| Reduction of gait variability; improvement of subjective ambulatory scores | |||||||
| Schniepp et al. [27] | DBN, SAOA, CACNA1A mutation, cerebellar stroke | 4-AP | 5 mg rid | Case series | – | 31 | Improvement of gait Increase of mean preferred gait velocity and mean cadence at preferred speed; decrease of the coefficient of variation of stride time |
| Giordano et al. [28] | SCA l,3,6,SAOA, POLG mutation | 4-AP-SR | Observational | 2 weeks | 16 | Modest short-term improvements mainly on gait and speech | |
| Improvements are within the range of placebo effects, long-term trials on prolonged effects are needed | |||||||
| NCT01811706 | SCA 1,2,3,6 | 4-AP-SR | 10 mg bid | Placebo-controlled | 4 weeks | – | Ongoing |
| FACEG | Cerebellar disorders of different etiology | 4-AP-SR | 10 mg bid | Placebo-controlled | 12 weeks | – | Ongoing |
Bid two time a day, tid three times a day, qid four time a day, DBN downbeat nystagmus, EA 2 episodic ataxia type 2, SAOA sporadic adult onset ataxia, SCA spinocerebellar ataxia, 4-AP 4-aminopyridine, SR slow release, 3,4-DAP 3,4-diaminopyridine