title: Narcolepsy-cataplexy: deficient prepulse inhibition of blink reflex suggests pedunculopontine involvement.
abstract: Hypocretin (orexin) deficiency plays a major role in the pathophysiology of narcolepsy-cataplexy. In animal models, hypocretinergic projections to the pedunculopontine nucleus are directly involved in muscle tone regulation mediating muscle atonia - a hallmark of cataplexy. We hypothesized that pedunculopontine nucleus function, tested with prepulse inhibition of the blink reflex, is altered in human narcolepsy-cataplexy. Twenty patients with narcolepsy-cataplexy and 20 healthy controls underwent a neurophysiological study of pedunculopontine nucleus function. Blink reflex, prepulse inhibition of the blink reflex and blink reflex excitability recovery were measured. Blink reflex characteristics (R1 latency and amplitude, and R2 and R2c latency and area under the curve) did not differ between patients and controls (P > 0.05). Prepulse stimulation significantly increased R2 and R2c latencies and reduced R2 and R2c areas in patients and controls. However, the R2 and R2c area suppression was significantly less in patients than in controls (to 69.8 ± 14.4 and 74.9 ± 12.6%, respectively, versus 34.5 ± 28.6 and 43.3 ± 29.5%, respectively; each P < 0.001). Blink reflex excitability recovery, as measured by paired-pulse stimulation, which is not mediated via the pedunculopontine nucleus, did not differ between patients and controls (P > 0.05). Our data showed that prepulse inhibition is reduced in narcolepsy-cataplexy, whereas unconditioned blink reflex and its excitability recovery are normal. Because the pedunculopontine nucleus is important for prepulse inhibition, these results suggest its functional involvement in narcolepsy-cataplexy.
authors.affiliation: Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Birgit
authors.initials: B
authors.lastname: Frauscher
authors.forename: Wolfgang N
authors.initials: WN
authors.lastname: Löscher
authors.forename: Laura
authors.initials: L
authors.lastname: Ehrmann
authors.forename: Viola
authors.initials: V
authors.lastname: Gschliesser
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Brandauer
authors.forename: Birgit
authors.initials: B
authors.lastname: Högl
authors.forename: Markus
authors.initials: M
authors.lastname: Kofler
mesh_terms: D000328:Adult; D000368:Aged; D001767:Blinking; D016022:Case-Control Studies; D002385:Cataplexy / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D045042:Pedunculopontine Tegmental Nucleus / Q000503:physiopathology*; D055815:Young Adult