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.
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