DOI: 10.1097/WNO.0b013e31824f397f

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PMID: 22487785

Issn Print: 1070-8022

Publication Date: 2012/06/01


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Aminopyridine Treatment in a Patient With Bilateral Vestibular Failure and Cryptogenic Downbeat Nystagmus

Rainer Spiegel; Roger Kalla; Jens Classen; Stanislavs Bardins; Fábio Anciães da Silva; Parvis Farahmand; Ales Hahn; Erich Schneider; Nicole Rettinger; Klaus Jahn; Thomas Brandt; Michael Strupp

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Author Information: LMU

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In a recent issue of this journal, Kalla et al (1) reported that 4-aminopyridine (4-AP) alleviates the symptoms of downbeat nystagmus (DBN) significantly more than 3,4-diaminopyridine (3,4-DAP). Both drugs are potassium-channel blockers, but 4-aminopyridine is lipid-soluble and more easily crosses the blood-brain-barrier. 3,4-diaminopyridine is not lipid soluble, with direct effects in the peripheral nervous system and indirect effects in the central nervous system via its metabolites (1,2). In the report by Kalla et al (1), 1 male patient suffered from bilateral vestibular failure (disorder of the peripheral nervous system) as well as DBN (disorder of the central nervous system). We now document this case in detail.
At the time of the study, the patient was 58 years old. Ten years earlier, he had traveled to Indonesia, where he suffered from extreme diarrhea with severe weight loss, followed by the development of tinnitus, oscillopsia, postural instability, and bilateral vestibular failure. MRI of the brain was normal. On examination, he was found to have DBN, which was documented with electronystagmography. The patient showed improvement of DBN following the administration of 3,4-DAP but not with 4-AP.
The reason for this finding might be that the effects of 3,4-DAP are more balanced between the peripheral and the central nervous systems, while the effects of 4-AP are primarily on the central nervous system. It had been suggested that the combination of bilateral vestibular failure and idiopathic DBN is due to a multisystem channelopathy, decreasing the calcium currents through P/Q channels and thus impacting potassium channels both in the peripheral and the central nervous systems (3–6). This multisystem channelopathy could explain disorders not only in the peripheral nervous system (such as bilateral vestibular failure) but also in the central nervous system (such as DBN). 3,4-DAP may restore the excitability of the cerebellar Purkinje cells at a similar pace as it restores peripheral functioning, hence stabilizing the feedback loop between their central effect on eye movements and their interaction with peripheral structures responsible for balance.

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