Cerebrospinal fluid-orexin levels and sleep attacks in four patients with Parkinson's disease.
OBJECTIVE
Sleep attacks (SAs) in Parkinson's disease (PD) are rare, but clinically important because they significantly impair the daily lives of patients. Causes of SAs include long-term activation of dopaminergic (especially D3) receptors. Recent studies suggest that SAs in PD may be related to impairment of hypothalamic orexin neurons, similar to narcolepsy. Whether orexin is associated with long-term activation of dopaminergic receptors remains uncertain.


METHODS
We measured levels of orexin in samples of spinal cerebrospinal fluid (CSF) from 25 patients with PD, including 9 with excessive daytime sleepiness and 4 with SAs. Furthermore, in the four patients with SAs, the selective dopamine D1/D2 agonist pergolide was substituted for the causative drugs with D3 stimulatory activity, and CSF-orexin levels were measured before and after switching treatment.


RESULTS
In the 25 patients with PD, including the 4 patients with SAs, lower CSF-orexin levels were associated with a longer disease duration, which has been linked to a higher incidence of SAs. Switching treatment to pergolide significantly increased CSF-orexin levels and completely resolved SAs in the four patients with PD.


CONCLUSIONS
Despite the small number of patients studied, our results suggest that orexin transmission is most likely involved in SAs in PD and that abrogation of D3 receptor stimulation may increase orexin and thereby inhibit SAs.
Asai
Hirohide
H
Department of Neurology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan. asaihozon@yahoo.co.jp
Hirano
Makito
M
Furiya
Yoshiko
Y
Udaka
Fukashi
F
Morikawa
Masami
M
Kanbayashi
Takashi
T
Shimizu
Tetsuo
T
Ueno
Satoshi
S
D000328:Adult; D000368:Aged; D018491:Dopamine Agonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000134:cerebrospinal fluid* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009479:Neuropeptides / Q000134:cerebrospinal fluid* / Q000378:metabolism; D000068797:Orexins; D010300:Parkinson Disease / Q000134:cerebrospinal fluid* / Q000188:drug therapy / Q000503:physiopathology; D010479:Pergolide / Q000008:administration & dosage / Q000494:pharmacology*; D011863:Radioimmunoassay; D017447:Receptors, Dopamine D1 / Q000819:agonists; D017448:Receptors, Dopamine D2 / Q000819:agonists; D050637:Receptors, Dopamine D3 / Q000378:metabolism; D012720:Severity of Illness Index; D012893:Sleep Wake Disorders / Q000134:cerebrospinal fluid* / Q000209:etiology* / Q000378:metabolism
D018491:Dopamine Agonists; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D010479:Pergolide