Hypocretin and human African trypanosomiasis.
OBJECTIVE
To detail clinical and polysomnographic characteristics in patients affected with Trypanosoma brucei gambiense (Tb.g.) human African trypanosomiasis (HAT) at different stages of evolution and to measure and compare cerebrospinal fluid (CSF) levels of hypocretin-1 with narcoleptic patients and neurologic controls.


METHODS
Twenty-five untreated patients affected with T.b.g. HAT were included. The patients were evaluated using a standardized clinical evaluation and a specific interview on sleep complaints. Diagnosis of stages I and II and intermediate stage was performed by CSF cell count and/or presence of trypanosomes: 4 patients were classified as stage II, 13 stage I, and 8 "intermediate" stage. Seventeen untreated patients completed continuous 24-hour polysomnography. We measured CSF levels of hypocretin-1 in all patients at different stages and evolutions, and we compared the results with 26 patients with narcolepsy-cataplexy and 53 neurologic controls.


RESULTS
CSF hypocretin-1 levels were significantly higher in T.b.g. HAT (423.2 +/- 119.7 pg/mL) than in narcoleptic patients (40.16 +/- 60.18 pg/ mL) but lower than in neurologic controls (517.32 +/- 194.5 pg/mL). One stage I patient had undetectable hypocretin levels and 1 stage II patient showed intermediate levels, both patients (out of three patients) reporting excessive daytime sleepiness but without evidence for an association with narcolepsy. No differences were found in CSF hypocretin levels between patients with HAT stages; however, the presence of major sleep-wake cycle disruptions was significantly associated with lower CSF hypocretin-1 level with a same tendency for the number of sleep-onset rapid eye movement periods.


CONCLUSIONS
The present investigation is not in favor of a unique implication of the hypocretin system in T.b.g. HAT. However, we propose that dysfunction of the hypothalamic hypocretin region may participate in sleep disturbances observed in African trypanosomiasis.
Dauvilliers
Yves
Y
Department of Neurology, University Hospital Gui de Chauliac, INSERM U888, Reference Centre for Narcolepsy, Montpellier France. y-dauvilliers@chu-montpellier.fr
Bisser
Sylvie
S
Chapotot
Florian
F
Vatunga
Gedeao
G
Cespuglio
Raymond
R
Josenando
Téofilo
T
Buguet
Alain
A
D000293:Adolescent; D000328:Adult; D000810:Angola; D000818:Animals; D002385:Cataplexy / Q000134:cerebrospinal fluid / Q000175:diagnosis; D005260:Female; D006801:Humans; D007031:Hypothalamus / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins / Q000134:cerebrospinal fluid*; D008297:Male; D008875:Middle Aged; D009290:Narcolepsy / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D009460:Neurologic Examination; D009479:Neuropeptides / Q000134:cerebrospinal fluid*; D000068797:Orexins; D017286:Polysomnography; D011863:Radioimmunoassay; D012016:Reference Values; D020178:Sleep Disorders, Circadian Rhythm / Q000134:cerebrospinal fluid / Q000175:diagnosis; D013223:Statistics as Topic; D014347:Trypanosoma brucei gambiense; D014353:Trypanosomiasis, African / Q000134:cerebrospinal fluid* / Q000175:diagnosis
C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins