Primary progressive narcolepsy type 1: The other side of the coin

Narcolepsy type 1 (NT1) is characterized by hypersomnolence associated with early occurrence of REM sleep (i.e., sleep-onset REM periods [SOREMP]) and cataplexy (i.e., sudden loss of muscle tone evoked by emotions), or with CSF hypocretin-1 (CSF hcrt-1) low levels (below 110 pg/mL, undetectable in most cases). Compelling evidence indicates that NT1 is caused by an autoimmune disease affecting HLA-DQB1*06:02 carriers.1 Diagnostic workup requires a history of cataplexy and multiple SOREMP at sleep studies (nocturnal polysomnography and multiple sleep latency test [MSLT]) or CSF hcrt-1 deficiency.2 At diagnosis, most patients with NT1 already have very reduced CSF hcrt-1 levels. Hypersomnolence and cataplexy presumably become evident when hypocretin cell loss is above 85%–90%, according to postmortem studies.3 A rapid and dramatically severe picture has been documented often in childhood-onset NT1, but it is also commonly recalled by history taking that the disorder can also slowly progress, and sleepiness may anticipate cataplexy by years. In full-blown NT1 cases, CSF hcrt-1 tends to maintain stable values through the disease course, and in only one case has CSF hcrt-1 been documented by chance before and after development of NT1, showing an abrupt step down from normal to pathologic values when the disease occurs.4 We document in an adult patient the slow onset of CSF hcrt-1 deficiency paralleled by a slow clinical progression to clear-cut NT1.