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 mo re 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 centr al 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 dec ay in delta power across the night. Cataplexy is associated with a dro p in H-reflex, even during partial cataplectic attacks. Monitoring of heart rate and intra-arterial blood pressure during cataplexy in human s shows a decrease in heart rate and an increase-in blood pressure wit h onset of cataplexy, but the change in heart rate is secondary to the change in blood pressure. Investigations of narcoleptic Doberman pins chers have implicated several neurotransmitters in the brainstem and a mygdala. In vivo dialysis and in situ injections of carbachol indicate that the pontine reticular formation is not the only muscarinic choli nergic region involved, but data support the existence of a multisynap tic descending pathway involved in the muscle atonia of cataplexy. Car bachol injections into the basal forebrain induce status cataplecticus . Experimental findings suggest a hypersensitivity of the overall musc arinic cholinergic system and that this hypersensitive cholinergic sys tem is linked to the limbic system. An increase in the postsynaptic D- 2 dopaminergic receptor is observed in the amygdala of narcoleptic dog s compared with controls, with impairment of dopamine release. The ass ociated findings suggest that an abnormal cholinergic-dopaminergic int eraction could underlie the pathophysiology of narcolepsy.