The clinical spectrum of narcolepsy with cataplexy: a reappraisal

In the absence of a golden standard for the diagnosis of narcolepsy, the clinical spectrum of disorder remains controversial. The aims of this study were (1) to determine frequency and characteristics of sleep-wake symptoms in patients with narcolepsy with cataplexy, (2) to compare clinical characteristics with results of ancillary tests, and (3) to identify factors that discriminate narcolepsy from other conditions with excessive daytime sleepiness (EDS). We prospectively studied 57 narcoleptics with cataplexy, 56 patients with non-narcoleptic hypersomnia (H), and 40 normal controls (No). Based on suggested and published criteria, we differentiated between narcoleptics with definite cataplexy (N) and narcoleptics without definite cataplexy (possible cataplexy, NpC). Assessment consisted of questionnaires [all patients and controls, including the Ullanlinna Narcolepsy Score (UNS)], polysomnography (all patients), multiple sleep latency test (MSLT) and human leukocyte antigen typing (in most narcoleptics). A new narcolepsy score based on five questions was developed. Data were compared with those of 12 hypocretin-deficient narcoleptics (N-hd). There were significant differences between N and NpC (including mean sleep latency on MSLT), but none between N and N-hd. A score of sleep propensity during active situations (SPAS) and the frequency of sleep paralysis/hallucinations at sleep onset, dreams of flying, and history of sleep shouting discriminated N from H and No (P < 0.001). Cataplexy-like symptoms in H (18%) and No (8%) could be discriminated from 'true' cataplexy in N on the basis of topography of motor effects, triggering emotions and triggering situations (P < 0.001). Our narcolepsy score had a similar sensitivity (96% versus 98%) but a higher specificity (98% versus 56%) than the UNS. Analysis of co-occurring symptoms in narcolepsy revealed two symptom complexes: EDS, cataplexy, automatic behaviors; and sleep paralysis, hallucinations, parasomnias. Low/undetectable cerebrospinal fluid hypocretin-1 levels and a history of definite cataplexy identify similar subgroups of narcoleptics. Specific questions on severity of EDS (SPAS score) and characteristics of cataplexy allow the recognition of subgroups of narcoleptics and their differentiation from non-narcoleptic EDS patients, including those reporting cataplexy-like episodes. The existence of co-occurring symptoms supports the hypothesis of a distinct pathophysiology of single narcoleptic symptoms.