Clinical And Electrophysiological Features In Narcolepsy Patients With Periodic Limb Movements During Sleep

Narcolepsy is a disorder primarily characterized by REM-sleep dissociation.Narcolepsy was known as excessive daytime sleepiness(EDS),accompanied typically by cataplexy attacks,and the symptoms associated with rapid eye movement sleep,such as sleep hallucinations and sleep paralysis,but only 50% have all four syndromes.It has now been firmly established that narcolepsy is defined two subtypes by deficiency of hypothalamic hypocretin(orexin)signaling or not,ICSD-3 notes Narcolepsy type 1 should be diagnosed when a defciency of hypothalamic hypocretin(orexin)signaling,also defined narcolepsy with cataplexy,without deficiency of hypocretin(orexin)was defined narcolepsy type 2,narcolepsy without cataplexy.Narcolepsy with cataplexy occurs in0.02% to 0.18% of the United States and western European populations.A lower prevalence has been reported in Israel,whereas narcolepsy with cataplexy may be slightly more common in Japan(0.16% to 0.18%).In our country,the prevalence of Narcolepsy with cataplexy is 0.033%.Over 50% patients are children and adolescents.Both sexes are affected,with a slight preponderance of males.The reduction in the number of hypocretin(orexin)neurons has been observed in brains obtained from narcoleptic donors.Hypocretin is an excitability neurotransmitter that is primarily secreted from the lateral hypothalamic neurons residing in the posterior hypothalamus.These neurons haveextensive excitability connections with the forebrain and brainstem,locating in Locus coeruleus nucleus,raphe nucleus,ventral tegmental area,nuclear,tegmentum dorsolateral tegmentum pons and nodules nipple nuclei.The strong HLA association in narcolepsy has led to the hypothesis that autoimmunity is a likely etiological mechanism,potentially explaining the selectivity of neuronal destruction in the hypothalamus.However,definitive proof for autoimmunity has not been obtained.PLMS is characterized by periodic episodes of repetitive,highly stereotyped limb movements that occur during sleep,in conjunction with clinical sleep disturbance or fatigue that cannot be accounted for by another primary sleep disorder or other etiology.PLMS occur most frequently in the lower extremities.They typically involve extension of the big toe,often in combination with partial flexion of the ankle,the knee,and sometimes,the hip.Similar movements can occur in the upper limbs.Dopaminergic impairment has been implicated in the pathophysiology of PLMS and PLMD.The study of PLMS in RLS and in children also suggests genetic diathesis and iron status as factors.1.2%-10% of children can be observed PLMSI>5,they didn’t verify in primary PLMS or RLS.Although the prevalence of children with other sleep disorders is increasing,the prevalence of PLMS in children is not well defined.As in adults,children with PLMS and narcolepsy have more sleep disruption and shorter mean sleep latency than those with narcolepsy but without PLMS.It may also suggest that PLMS are a feature of more severe narcolepsy.Adult narcolepsy patients with PLMS have been shown to have more impairment of daytime functioning than those without PLMS,in that those with PLMS have a shorter mean sleep latency than those without,suggesting greater sleepiness.Furthermore,in adult a higher PLMSI has been shown to be associated with a higher PLM when awake index,suggesting greater disruption of daytime functioning.Objectives:The aim of the present study was to investigate the difference between N+PLMS and N-PLMS:disrupted nighttime sleep or not,excessive daytime sleepiness was more severe or not,clinical characteristics was more or not;Clinical and Electrophysiological features between children-adolecents and adults,between N+C and N-C.The difference of subjective and objective sleepiness in narcolepsy patients.Methods:We collected patients who have been diagnosed with narcolepsy in our center from January 2015 to December 2016.These patients were divided into three groups:narcolepsy patients with PLMS(N+PLMS)(n=18),narcolepsy patients without PLMS(N-PLMS)(n=76);children-adolecents(age<18 years,n=41)and adults(age≥18 years,n=53);N+C(n=74)and N-C(n=20).We compared the different points on PSG and MSLT.Epworth Sleepiness Scale(ESS)is followed by PSG and MSLT,which is used for subjective and objective sleepiness.Results:1.In all 94 narcolepsy patients,female 28(29.8%),male 66(70.2%),the ratio was2.36:1.Children and adolescent capture the peak,the distribution of age was from 5 to20(53.2%).2.N+C 74(78.7%),N-C 20(21.3%).Excessive daytime sleepiness 9(100%),cataplexy attacks74(78.7%),sleep paralysis 22(23.4%),hypnagogic/hypnopompic hallucinations36(38.3%),RBD52(55.3%),OSA28(29.8%).In their subjective syndromes,sleep maintenance dysfunction 33(35.1%),dreamful sleep 58(61.7%)in nighttime sleep,whereas,in daytime discomforts,anxiety 24(25.5%),hypothymergasia 30(31.9%),fatigue 45(47.9%),and the impaired ability of study and work 34(36.2%).ESS(14.3±5.5).3.N+PLMS was 18(19.1%),children and adolescent captured the peak,especially 6-10 years old.Between the(N+PLMS)group and(N-PLMS)group:lower BMI(t=-2.321,P=0.023)、 more RBD(c 2=4.543,P=0.033)、 more WASO(z=-2.061,P=0.039)、 more times of arousal episode longer than 5minutes(z=-3.069,P=0.002)、 and more sleep times in MSLT(z=-2.130,P=0.033)are significant difference.There was no significant difference between PLMSI and ESS(r=1.104,P=0.320).There was significant difference between PLMSI and sleep times in MSLT(r=-0.238,P=0.021).4.Children-adolecents(age<18 years,n=41)and adults(age≥18 years,n=53):longer course of disease(z=-3.339,P=0.001),more BMI(t=-5.764,P=0.000),more WHR(t=-2.610,P=0.011)、ESS(t=-4.898,P=0.000),more hypnagogic/hypnopompic hallucinations(c2=8.223,P=0.004)、more RBD(c2=4.952,P=0.026),more N1%(z=-2.680,P=0.009)、more N2%(z=-2.474,P=0.015)、less N3%(z=8.224,P=0.000),more arousal index(z=-3.115,P=0.002)and more AHI(z=-3.997,P=0.000)was significant difference(P<0.05).5.N+C and N-C:There was significant difference in more RBD(c2=6.589,P=0.010)、more WASO(z=-2.374,P=0.018),ore times of arousal episode longer than 5minutes(z=-2.699,P=0.007)、 shorter the second to fifth sleep latency(z=-3.510,P=0.000;z=-2.436,P=0.015;z=-1.987,P=0.029;z=-2.672;P=0.008),less sleep times(z=-1.975,P=0.037),shorter MSL(z=-3.427,P=0.001)and less SOREMPs(z=-2.344,P=0.019).6.The correlation of subjective and objective in narcolepsy:There was significant difference in ESS and MSL(r=-0.298,P=0.003),the fourth to fifth sleep latency(r=-0.248,P=0.017;r=-0.231,P=0.027).There was significant difference between ESS and MSL(r=-0.424,P=0.031).Conclusions:1.The ratio of male to female is 2.36:1.Children and adolecents captured the peak of onset age.Four essential syndromes was 33%,at the same time,Associated Features and daytime dysfunction were also manifested.2.PLMS was common in narcolepsy,especially in children and adolecents,PLMS can disrupt nighttime sleep and worsen sleepiness;RBD was common in narcolepsy with PLMS.3.Adults had longer course of disease,BMI,WHR and hypnagogic/hypnopompic hallucinations,but children and adolecents had more RBD.N+C had more RBD,disrupted nighttime and daytime sleepiness than N-C.4.We can combine ESS and MLST to evaluate subjective and objective sleepiness for better diagnose and treatment.