Investigations into the neurologic basis of narcolepsy.
The understanding of narcolepsy has been enhanced by neurophysiologic investigations in humans and by pharmacologic and biochemical studies using the canine model of narcolepsy. Repetitive microsleeps have a more deleterious effect on performance than several short complete naps during the day. Under normal living conditions, the nocturnal sleep of narcoleptic patients is disrupted, and the spectral analysis of central EEG leads shows less delta power density per epoch than it does in age-matched controls, who have an absence or decrease of the usual decay in delta power across the night. Cataplexy is associated with a drop in H-reflex, even during partial cataplectic attacks. Monitoring of heart rate and intra-arterial blood pressure during cataplexy in humans shows a decrease in heart rate and an increase in blood pressure with onset of cataplexy, but the change in heart rate is secondary to the change in blood pressure. Investigations of narcoleptic Doberman pinschers have implicated several neurotransmitters in the brainstem and amygdala. In vivo dialysis and in situ injections of carbachol indicate that the pontine reticular formation is not the only muscarinic cholinergic region involved, but data support the existence of a multisynaptic descending pathway involved in the muscle atonia of cataplexy. Carbachol injections into the basal forebrain induce status cataplecticus. Experimental findings suggest a hypersensitivity of the overall muscarinic cholinergic system and that this hypersensitive cholinergic system is linked to the limbic system. An increase in the postsynaptic D2 dopaminergic receptor is observed in the amygdala of narcoleptic dogs compared with controls, with impairment of dopamine release. The associated findings suggest that an abnormal cholinergic-dopaminergic interaction could underlie the pathophysiology of narcolepsy.
Guilleminault
C
C
Stanford University Sleep Disorders Clinic and Research Center, Palo Alto, CA, USA.
Heinzer
R
R
Mignot
E
E
Black
J
J
D000818:Animals; D001327:Autoimmune Diseases; D001342:Autonomic Nervous System Diseases / Q000150:complications*; D001927:Brain Diseases / Q000150:complications*; D004195:Disease Models, Animal; D004569:Electroencephalography; D006801:Humans; D009290:Narcolepsy / Q000209:etiology* / Q000503:physiopathology