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Spiegel, Rainer (2011): Downbeat nystagmus: changes during daytime and its treatment. Dissertation, LMU München: Medizinische Fakultät



In this thesis, three aspects of downbeat nystagmus (DBN) were examined. First, changes of its intensity during daytime; second, an analysis of the underlying mechanisms, in particular, the modulation of otolith input; and third, the effects of a pharmacotherapy with potassium channel blockers 4-aminopyridine in comparison with 3,4-diaminopyridine. Downbeat nystagmus consists of ocular drifts upwards. These upward drifts cannot be deliberately controlled. As a correcting mechanism, the upward drifts are followed by downward saccades. Downbeat nystagmus is either due to lesions in the cerebellum, due to lesions to the brainstem or due to cryptogenic/idiopathic causes. In order to reduce symptoms effectively, it is of particular importance to increase our knowledge about DBN. In chapter 1 of this thesis it is shown that the intensity of DBN decreases during daytime. In chapter 2, it is demonstrated that resting positions have an influence on the extent of DBN. During daytime, where people are generally in upright body position, DBN decreases effectively when people remain upright during their resting periods, i.e. when people sit instead of lying down to rest. There is a possible reason why DBN in upright position significantly decreases when people rest upright. This could have been due to otoliths exerting a stabilizing influence on the central vestibular neurons of the patients while remaining upright for a continuous period. Moreover, it does not make a difference whether patients with DBN rest with the light switched on or with the light switched off. Chapters 1 and 2 also have implications for symptomatic treatment. It can be suggested to patients to rest in an upright position during the day, and to engage in activities such as reading or screen-related work in the afternoon rather than in the morning. In chapter 3, another way of symptom reduction is presented, where the aminopyridines 4-AP and 3,4-DAP are compared against each other. The efficacy of reducing DBN had previously been demonstrated individually for both aminopyridines. In this thesis, the efficacy of both aminopyridines was examined in a double-blind study with cross-over design. The major finding was that 4-AP is more effective than 3,4-DAP in terms of reducing the intensity of DBN. Moreover, 4-AP revealed a tentative trend towards a particular efficacy for cerebellar patients, which is in line with experimental evidence, where it had been reported to better cross the blood-brain barrier and to have at least the same (probably even a longer) half-life than 3,4-DAP. In conclusion, no causative treatment is in sight for DBN, but clinical studies can lead to a better understanding of DBN and may contribute to symptom alleviation.