Narcolepsy

(Gelineau syndrome)

Rare: estimated prevalence of 4/10,000 in Europa and North America. Chronic disorder of sleep. Chronic neurological disease characterized by attacks of irresistible sleep often associated with hypnogogic hallucinations (= when falling asleep) or hypnopompic hallucinations (= when waking up), and a feeling of paralysis when waking up. These sleep attacks usually start between 10 and 30 years of age and are sometimes accompanied by/preceeded by a sharp increase in weight with overeating or precocious puberty. Sometimes the signs of narcolepsy are therefore attributed to obstructive sleep apnea syndrome.

Different forms:

-        narcolepsy type 1 with a cataplexy (sudden loss of muscle tone), and insufficient level of hypocretin-1 < 110 pg/ml (normal: > 200 pg/ml) [MIM 161 400, 605 841, 609 039, 612 417, 612 851, 614 223, 614 250]

-        narcolepsy type 2 without cataplexy and a level of hypocretin-1 > 110 pg/ml.

Polysomnography shows a dysregulation of REM sleep: the average sleep latency is less than 8 minutes and sleep in REM stage during daytime crises. There is a close association with the HLA antigen DBQ1*062 in 95% of patients who suffer from narcolepsy type 1 and 41% of the patients who suffer from narcolepsy type 2; this HLA antigen is only present in 18-35% of the normal population. Other genetic factors (including mutations in the genes of monoamine oxidase MAO,  catechol-o-methyltransferase COMT, carnitine palmitoyl transferase1b CPT1B, or choline kinase beta CHBK) are probably involved, and it is possible that an autoimmune component explains progressive necrosis of the hypocretin-secreting neurons. A few cases have been associated with anti-H1N1 vaccination.

Cases of secondary narcolepsy have been reported in the postoperative period following neurosurgical interventions on the hypothalamus or the fourth ventricle.


Epworth sleepiness scale



Treatment:

-        amphetamines: methylphenidate

-        or modafinil and armodafinil:  the unknown mechanism of action probably involves inhibition of reuptake of dopamine; it inhibits cytochrome CYP2C9

-        sodium oxybate that decreases the frequency of episodes of cataplexy but can exacerbate obstructive sleep apnea syndrome; it is a GABAB agonist that blocks the GHB receptors, one of the GABA metabolites.


Anesthetic implications:

the treatment should be continued until the operating day; monitoring of the depth of anesthesia (BIS or other device); prefer locoregional anesthesia technique (it does not protect against peroperative narcolepsy episodes) or short acting opioids and multimodal analgesia; obstructive sleep apnea; obesity. There seems to be no peculiarities from the anesthetic point of view, but there could be an increased risk of postoperative hemodynamic problems. In case of treatment with modafinil: risk of delayed emergence in case of total IV anesthesia with propofol (inhibition of the metabolism of propofol ?) but apparent resistance to propofom during induction of anesthesia ?


References : 


Updated: January 2018