The publisher's final edited version of this article is available at Cerebellum
See other articles in PMC that cite the published article.
Treatment of motor symptoms of degenerative cerebellar ataxia remains difficult. Yet there are recent developments that are likely to lead to significant improvements in the future. Most desirable would be a causative treatment of the underlying cerebellar disease. This is currently available only for a very small subset of cerebellar ataxias with known metabolic dysfunction. However, increasing knowledge of the pathophysiology of hereditary ataxia should lead to an increasing number of medically sensible drug trials. In this paper, data from recent drug trials in patients with recessive and dominant cerebellar ataxias will be summarized.
There is consensus that up to date, no medication has been proven effective.
Aminopyridines and acetazolamide are the only exception, which are beneficial in patients with episodic ataxia type 2. Aminopyridines are also effective in a subset of patients presenting with downbeat nystagmus. As such, all authors agreed that the mainstays of treatment of degenerative cerebellar ataxia are currently physiotherapy, occupational therapy, and speech therapy.
For many years, well-controlled rehabilitation studies in patients with cerebellar ataxia were lacking. Data of recently published studies show that coordinative training improves motor function in both adult and juvenile patients with cerebellar degeneration. Given the well-known contribution of the cerebellum to motor learning, possible mechanisms underlying improvement will be outlined. There is consensus that evidence-based guidelines for the physiotherapy of degenerative cerebellar ataxia need to be developed. Future developments in physiotherapeutical interventions will be discussed including application of non-invasive brain stimulation.
Keywords: Cerebellum, Cerebellar ataxia, Motor rehabilitation, Physiotherapy, Drug therapy
11. Strupp M, Kalla R, Dichgans M, Freilinger T, Glasauer S, Brandt T. Treatment of episodic ataxia type 2 with the potassium channel blocker 4-aminopyridine. Neurology. 2004;62:1623–5. [PubMed]
12. Alvina K, Khodakhah K. The therapeutic mode of action of 4-aminopyridine in cerebellar ataxia. J Neurosci. 2010;30:7258–68. [PMC free article][PubMed]
13. Weisz CJ, Raike RS, Soria-Jasso LE, Hess EJ. Potassium channel blockers inhibit the triggers of attacks in the calcium channel mouse mutant tottering. J Neurosci. 2005;25:4141–5. [PubMed]
14. Claassen J, Teufel J, Kalla R, Spiegel R, Strupp M. Effects of dalfampridine on attacks in patients with episodic ataxia type 2: an observational study. J Neurol. 2013;260:668–9. [PubMed]
15. Hufner K, Stephan T, Kalla R, Deutschlander A, Wagner J, Holtmannspotter M, et al. Structural and functional MRIs disclose cerebellar pathologies in idiopathic downbeat nystagmus. Neurology.2007;69:1128–35. [PubMed]
16. Wagner JN, Glaser M, Brandt T, Strupp M. Downbeat nystagmus: aetiology and comorbidity in 117 patients. J Neurol Neurosurg Psychiatry. 2008;79:672–7. [PubMed]
17. Kalla R, Deutschlander A, Hufner K, Stephan T, Jahn K, Glasauer S, et al. Detection of floccular hypometabolism in downbeat nystagmus by fMRI. Neurology. 2006;66:281–3. [PubMed]
18. Kalla R, Glasauer S, Buttner U, Brandt T, Strupp M. 4-Aminopyridine restores vertical and horizontal neural integrator function in downbeat nystagmus. Brain. 2007;130:2441–51. [PubMed]
19. Tsunemi T, Ishikawa K, Tsukui K, Sumi T, Kitamura K, Mizusawa H. The effect of 3,4-diaminopyridine on the patients with hereditary pure cerebellar ataxia. J Neurol Sci. 2010;292:81–4.[PubMed]
20. Kalla R, Spiegel R, Claassen J, Bardins S, Hahn A, Schneider E, et al. Comparison of 10-mg doses of 4-aminopyridine and 3,4-diaminopyridine for the treatment of downbeat nystagmus. J Neuroophthalmol.2011;31:320–5. [PubMed]
21. Judge SI, Bever CT., Jr Potassium channel blockers in multiple sclerosis: neuronal Kv channels and effects of symptomatic treatment. Pharmcol Ther. 2006;111:224–59. [PubMed]
22. Claassen J, Spiegel R, Kalla R, Faldon M, Kennard C, Danchaivijitr C, et al. A randomised double-blind, cross-over trial of 4-aminopyridine for downbeat nystagmus—effects on slowphase eye velocity, postural stability, locomotion and symptoms. J Neurol Neurosurg Psychiatry. 2013 doi: 10.1136/jnnp-2012-304736. [PubMed][Cross Ref]
23. Feil K, Claaβen J, Bardins S, Teufel J, Krafczyk S, Schneider E, et al. Effect of chlorzoxazone in patients with downbeat nystagmus: a pilot trial. Neurology. 2013;81:1152–8. [PubMed]
24. Averbuch-Heller L, Tusa RJ, Fuhry L, Rottach KG, Ganser GL, Heide W, et al. A double-blind controlled study of gabapentin and baclofen as treatment for acquired nystagmus. Ann Neurol.1997;41:818–25. [PubMed]
25. Schniepp R, Jakl V, Wuehr M, Havla J, Kumpfel T, Dieterich M, et al. Treatment with 4-aminopyridine improves upper limb tremor of a patient with multiple sclerosis: a video case report. Mult Scler. 2013;19:506–8. [PubMed]
26. Schniepp R, Wuehr M, Ackl N, Danek A, Brandt T, Strupp M, et al. 4-Aminopyridine improves gait variability in cerebellar ataxia due to CACNA 1A mutation. J Neurol. 2011;258:1708–11. [PubMed]
27. Schniepp R, Wuehr M, Neuhaeusser M, Benecke AK, Adrion C, Brandt T, et al. 4-Aminopyridine and cerebellar gait: a retrospective case series. J Neurol. 2012;259:2491–3. [PubMed]
28. Giordano I, Bogdanow M, Jacobi H, Jahn K, Minnerop M, Schoels L, et al. Experience in a short-term trial with 4-aminopyridine in cerebellar ataxia. J Neurol. 2013;260:2175–6. [PubMed]
29. Etzion Y, Grossman Y. Highly 4-aminopyridine sensitive delayed rectifier current modulates the excitability of guinea pig cerebellar Purkinje cells. Exp Brain Res. 2001;139:419–25. [PubMed]
30. Hourez R, Servais L, Orduz D, Gall D, Millard I, de Kerchove d'Exaerde A, et al. Aminopyridines correct early dysfunction and delay neurodegeneration in a mouse model of spinocerebellar ataxia type 1. J Neurosci. 2011;31:11795–807. [PubMed]