Development of Parkinson and Alzheimer Diseases in Two Cases of Narcolepsy-Cataplexy

Abstract

Case 1 A 69-year-old Caucasian male, suffering from NC since the age of 17, presented to us at the age of 64 years (in 2006). His history included EDS with sleep attacks, hallucinations, frequent cataplexy and occasional sleep paralysis. Patient’s psychomotor development was normal and clinical history unremarkable; in particular, he denied infectious or inflammatory cerebral diseases, head trauma and exposure to toxic agents. During his NC history, the patient underwent several drug treatments (methylphenidate, modafinil, dexedrine, imipramine) with partial benefit on EDS and cataplexy. At that time, he presented the typical HLA haplotype (HLA DQB1 * 0602), undeDear Sir, Narcolepsy (NC) is a sporadic hypersomnia (prevalence 1: 2,000), characterized by excessive daytime sleepiness (EDS) and sleep attacks, typically associated with cataplexy and other REM-sleep related phenomena such as sleep paralysis and hallucinations [1] . In human NC with cataplexy, an association with specific HLA haplotype (DR DQB1 0602) and a deficiency in hypocretin (orexin) peptide in cerebrospinal fluid (CSF) are almost constant findings. The pathogenesis of human NC is still unknown. Autoimmune and neurodegenerative processes of hypothalamic structures have been discussed with more solid evidence for the first theory [2–4] . Most of narcoleptic symptoms develop early after the onset of the disease and usually do not worsen with the progression of the neurodegeneration [2] . Moreover, the absence of ubiquitinated inclusions (cardinal neuropathological finding of most neurodegenerative diseases) in narcoleptic patients argues against the neurodegenerative hypothesis in NC [3] . An autoimmune process involving the hypocretin neurons of lateral hypothalamus has been postulated [4] . There are few reports in the literature showing the occurrence of NC-like symptoms in patients already affected by Parkinson’s disease (PD) and other neurodegenerative diseases [2, 5–7] . Hypocretin neuronal loss has been documented in Received: July 18, 2011 Accepted: October 30, 2011 Published online: December 10, 2011