Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028738 (nystagmus)
 7,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Downbeat nystagmus (DBN) is a common, usually persistent ocular motor sign in vestibulocerebellar midline lesions. Postural imbalance in DBN may increase on lateral gaze when downbeat nystagmus increases. 3,4-Diaminopyridine (3,4-DAP) has been shown to suppress the slow-phase velocity component of downbeat nystagmus and its gravity-dependent component with concomitant improvement of oscillopsia. Because the pharmacological effect is thought to be caused by improvement of the vestibulocerebellar Purkinje cell activity, the effect of 3,4-DAP on the postural control of patients with downbeat nystagmus syndrome was examined. Eye movements were recorded with the video-based Eyelink II system. Postural sway and pathway were assessed by posturography in lateral gaze in the light and on eye closure. Two out of four patients showed an improvement of the area of postural sway by 57% of control (baseline) on eye closure. In contrast, downbeat nystagmus in gaze straight ahead and on lateral gaze did not benefit in these two patients, implying a specific influence of 3,4-DAP on the vestibulocerebellar control of posture. It was concluded that 3,4-DAP may particularly influence the postural performance in patients with downbeat nystagmus.
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PMID:Effect of 3,4-diaminopyridine on the postural control in patients with downbeat nystagmus. 1582 92

3,4-Diaminopyridine (3,4-DAP) is a potassium channel blocker that has recently demonstrated an antioscillatory effect in humans by significantly reducing downbeat nystagmus. Based on the presumed role of intrinsic oscillations in the pathophysiology of essential tremor (ET), the authors conducted a double-blind, placebo-controlled crossover study assessing the antitremor effect of a single dose of 3,4-DAP in 19 patients with ET. They did not find any significant change in tremor severity as measured by clinical ratings or accelerometry.
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PMID:No benefit of 3,4-diaminopyridine in essential tremor: a placebo-controlled crossover study. 1676 57

Downbeat nystagmus (DBN) is the most frequent form of acquired persisting fixation nystagmus. It is hypothesized to occur when physiological inhibitory cerebellar input, namely of the flocculus, to the vestibular nuclei is inhibited. The second most frequent form of acquired nystagmus is upbeat nystagmus (UBN). UBN is probably caused by an imbalance of vertical vestibulo-ocular reflex tone. GABA-ergic substances like baclofen have been used to treat DBN and UBN, but they have had only moderate success. Animal experiments have shown that aminopyridines [3,4-diaminopyridine (3,4-DAP) and 4-aminopyridine (4-AP)], nonselective blockers of the Kv family of voltage-gated potassium channels, increase Purkinje-cell (PC) excitability. It was assumed that such enhancement of PC activity could restore to normal levels the inhibitory influence of the cerebellar cortex on vertical eye movements. On the basis of these assumptions, we evaluated the efficacy and underlying mechanisms of aminopyridines in DBN and UBN as well as in another cerebellar disorder with an impaired PC function: episodic ataxia type 2 (EA2), which is caused by mutations of the PQ-calcium channel. In a placebo-controlled trial on 17 patients we demonstrated that 3,4-DAP significantly reduces the intensity of DBN. This was confirmed in a recent study with 4-AP, which also showed that 4-AP restores gaze-holding ability independently of fixation in DBN. The efficacy of 4-AP in UBN was demonstrated in single patients. Finally, in an open trial on three patients with EA2 we showed that 4-AP prevents attacks of ataxia. This was also found in an animal model (the tottering mouse) of EA2. The clinical efficacy of 4-AP in EA2 is being further evaluated in an ongoing randomized controlled crossover trial. In conclusion, the use of aminopyridines in DBN, UBN, and EA2 is a new treatment principle for vestibular, cerebellar, and ocular motor disorders.
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PMID:Aminopyridines for the treatment of cerebellar and ocular motor disorders. 1871 50