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Polysomnographic and Clinical Findings in Subjectswith Recurrent Isolated Sleep Paralysis

Polysomnographische und klinische Befunde bei Personen mit wiederkehrender isolierterSchlaflahmung

Bjorn W. Walther and Hartmut SchulzDepartment of Neurology, HELIOS Klinikum Erfurt, Erfurt, Germany

Summary Question of the study Sleep paralysis is one of the typical symptoms of narcolepsy, found in

about 25% of narcoleptic patients. It also represents a separate sleep disorder classified as a

REM sleep-related parasomnia. We compared clinical and electrophysiological data of

patients with recurrent isolated sleep paralysis (RISP) with those of narcoleptic patients and

healthy control subjects.

Patients and methods Structured interview data, polygraphic sleep recording, Multiple

Sleep Latency Test (MSLT) and human leukocyte antigen (HLA) DR2(15) typing were

compared in sex- and age-matched patients with RISP (n ¼ 10, mean age: 48.2 years, 4

males/6 females), narcolepsy (NAR, n ¼ 10, mean age: 51.5 years, 4 males/6 females) and

healthy controls (CON, n ¼ 10, mean age: 51.5 years, 5 males/5 females).

Results Night sleep latencies were prolonged in RISP (mean: 40.6 ± 25.3 min; NAR:

19.5 ± 8.8 min; CON: 19.2 ± 15.6 min). No sleep onset REM (SOREM) episodes (latency

<20 min) were observed in RISP patients, and short (<50 min) REM sleep latencies were

rare. In some cases REM sleep episodes were fragmented or abbreviated. The distribution of

REM latencies was largely inconspicuous. The distribution of NREM sleep stages was

normal. In the MSLT, latencies for sleep stages 1 and 2 were longer in RISP than in

narcoleptic patients, and while SOREM phases were abundant in narcoleptic patients, such

events were extremely rare in RISP patients. Daytime sleepiness, assessed by the Epworth

Sleepiness Scale (ESS), did not differ between RISP (median: 9) and CON (median: 6.5) but

was significantly increased in NAR (median: 20.5). HLA typing showed that seven out of 10

RISP patients were HLA DR2(15) negative. None of the patients with RISP had ever

experienced cataplectic attacks.

Conclusions RISP and NAR patients differ in critical HLA alleles and in key sleep variables

such as sleep latency and REM latency. According to our findings, SOREM episodes are not

a typical feature of RISP. In contrast to other studies, RISP patients do not show excessive

daytime sleepiness compared with healthy controls.

Keywords isolated sleep paralysis – sleep latency – REM latency – HLA typing – MSLT.

Zusammenfassung Fragestellung Die Schlaflahmung ist ein typisches Symptom der Narkolepsie und findet

sich bei etwa 25% der narkoleptischen Patienten. Sie stellt aber auch eine eigenstandige

Schlafstorung dar, die als REM-Schlaf bezogene Parasomnie klassifiziert wird. Wir

verglichen klinische und elektrophysiologische Daten von Patienten mit wiederkehrender

isolierter Schlaflahmung (RISP) mit denen narkoleptischer Patienten und gesunder

Kontrollpersonen.

S O M 0 1 7 B Dispatch: 19.3.04 Journal: SOM CE: Blackwell

Journal Name Manuscript No. Author Received: No. of pages: 9 PE: Saravanan

Correspondence: Dr. Bjorn W. Walther, Department of Neurology, HELIOS Klinikum Erfurt, PO Box 101263, 99012 Erfurt, Germany.

E-mail: bwalther@erfurt.helios-kliniken.de

Received: 22.01.04 ⁄Accepted: 01.03.04

� 2004 Blackwell Verlag, Berlin www.blackwell-synergy.com

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Patienten und Methodik Die Ergebnisse eines strukturierten Interviews, Fragebogendaten,

polysomnographische Aufzeichnungen, Multipler Schlaflatenz-Test (MSLT) und HLA

DR2(15) Befunde wurden verglichen fur nach Alter und Geschlecht angepassten Patienten

mit RISP (n ¼ 10; mittleres Alter 48,2 Jahre; 4 Manner, 6 Frauen), Narkolepsie (NAR,

n ¼ 10; mittleres Alter 51,5 Jahre; 4 Manner, 6 Frauen) und gesunde Kontrollen (CON,

n ¼ 10; mittleres Alter 51,5 Jahre; 5 Manner, 5 Frauen).

Ergebnisse Die nachtlichen Schlaflatenzen waren fur RISP verlangert (Durchschnittswerte:

RISP 40,6 ± 25,3 Minuten; NAR 19,5 ± 8,8 Minuten; CON 19,2 ± 15,6 Min). Die

Verteilung der REM-Latenzen war weitgehend unauffallig. Bei RISP wurden keine

Einschlaf-REM-Episoden (Latenz <20 Minuten) beobachtet und kurze (<50 Minuten)

REM-Latenzen waren selten. In einigen Fallen waren REM-Schlaf-Episoden fragmentiert

oder verkurzt. Die Verteilung der NREM-Schlafstadien war normal. Im MSLT waren die

Schlaflatenzen fur die Stadien 1 und 2 bei RISP langer als bei narkoleptischen Patienten, und

wahrend Einschlaf-REM-Episoden bei narkoleptischen Patienten sehr haufig auftraten,

waren solche Ereignisse bei Patienten mit RISP ausgesprochen selten. Tagesschlafrigkeit,

gemessen mit der Epworth Schlafrigkeitsskala (ESS), unterschied sich nicht zwischen RISP

(Median 9 Punkte) und CON (Median 6,5 Punkte), war bei NAR allerdings signifikant erhoht

(Median 20,5 Punkte). Bei der HLA-Typisierung waren 7 von 10 Patienten mit RISP DR

2(15) negativ.

Schlussfolgerungen Patienten mit RISP und Narkolepsie unterscheiden sich in kritischen

HLA-Allelen und in Schlusselvariablen des Schlafs wie Schlaflatenz und REM-Latenz. Nach

den Ergebnissen unserer Untersuchungen sind Einschlaf-REM-Episoden fur RISP kein

typisches Merkmal. Entgegen anderer Studien zeigen RISP-Patienten keine erhohte

Tagschlafneigung im Vergleich zu gesunden Kontrollen.

Schlusselworter isolierte Schlaflahmung – Schlaflatenz – REM-Latenz – HLA-Typisie-

rung – MSLT.

Introduction

Moses Mendelssohn (1729–86), a Jewish philosopher andcontemporary of Ephraim Lessing, who dedicated the drama‘Nathan the Wise’ to him, gave a lively description of hisown experience with sleep paralysis when he wrote:‘During the attacks, which were in the habit of coming

over me on waking from a restless sleep, I was completelyconscious, was able to follow each chain of thought Iresolved to make, in order and with clarity, just that I wasincapable of any voluntary movement, could move neither alimb of my body, nor could I make a sound or open my eyes;and each effort I made, any limb to move, was completelyfruitless and only increased the very adverse sensation whichaccompanied the condition. It was namely as if somethingglowing hot wanted to pour out of my brain down my spineand met with resistance or as if somebody whipped my neckwith glowing rods. Therefore I had to keep completely still,until an outside impression opened as it were the sluices forlife to flow back into me again; and then in the same momenteverything was restored and I was master of my voluntarymovements again.’ (quoted from [16, pp. 41–42], owntranslation)One of the most comprehensive descriptions of the

disorder was published by John Waller in 1816 under thetitle A Treatise on the Incubus, or Night Mare, Disturbed

Sleep, Terrific Dreams, and Nocturnal Visions. With themeans of removing these distressing complaints [28]. Waller,a ship’s doctor to the British fleet, was himself plagued withrecurrent sleep paralysis. In his book he gave a vividdescription of the different symptoms accompanying sleepparalysis such as shortness of breath, tachycardia, palpitation,atony and priapism. Waller also suggested an associationbetween sleep paralysis and the personality and psychopa-thology of afflicted persons.

Sleep paralysis (SP) is defined as an inability to move, inthe sense of feeling paralysed during the transition to sleep oron awakening from sleep. SP is experienced by about 25% ofpatients suffering from narcolepsy [31]. The isolated form ofsleep paralysis (ISP) was classified in the InternationalClassification of Sleep Disorders as a parasomnia associatedwith REM sleep [14].The pathophysiology of sleep paralysis is still poorly

understood [13]. Takeuchi et al. succeeded in eliciting ISPepisodes by deliberate sleep interruptions in normal subjects[26, 27]. The polygraphic recording during an ISP episodewas characterized either by intrusion of alpha EEG activity inREM sleep or by the persistence of REM atony afterawakening, a sign of dissociation or overlap of REM sleepand the waking state. To the best of our knowledge, these arethe only polygraphic data in the literature on SP. Buzzi andCirignotta assumed a pathophysiological analogy of recur-rent ISP to the ion channel disorders, and the stereotypicalsubjective experiences were explained by these authors as anactivation of the limbic system [3].Singular or occasional episodes of ISP were reported in

questionnaire studies with a high prevalence in Japanese(39.8%) [11], Chinese students (37%) [30], black subjects(40%) [2], in two samples of Nigerian students (26.1% and44%) [19,20], Canadians (30%) [5], and in people living inNewfoundland (62%) [18]. Lower prevalence rates werereported for samples of students from Europe (15.4%) [8] andNorth America (16.4%) [23]. More recently, Ohayon et al.found that ISP was less common (overall 5.7–6.7%) in thegeneral population, based on representative samples fromGermany and Italy, respectively [21]. Anxiety and psychicstress may be triggering factors in ISP episodes [20]. In thestudy by Ohayon et al., predictive variables for ISP wereanxiolytic medication, automatic behaviour, bipolar disor-

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ders, physical disease, hypnopompic hallucinations, non-restorative sleep, and nocturnal leg cramps [21]. Theprevalence of SP seems to be higher in subjects with a panicdisorder or a high neuroticism score [10, 22]. There are fewdata dealing with the prevalence of recurrent ISP (RISP) as achronic complaint. Surveys of normal subjects have indicatedRISP in 3–6% [14], but many of the respondents had onlyrare episodes. However, new data from a web survey suggesta higher prevalence, acknowledging that only eight out of110 subjects with recurrent and disabling attacks of ISPcontacted a physician [3].Dahlitz and Parkes [6] compared 22 patients who suffered

from frequent episodes of SP and excessive daytimesleepiness (EDS) with 42 patients who showed the samesymptoms in combination with cataplexy. Patients with SPhad a lower mean score on the Epworth Sleepiness Scale [15]than those with SP and cataplexy, and the former group ofpatients did not show an association with HLA haplotypesDR2(15) or DQ1(6). The authors concluded that ‘sleepparalysis/excessive daytime sleepiness syndrome withoutcataplexy is not a subtype of the narcoleptic syndrome, but aseparate disorder’ [6, p. 407].In the last 5 years, we have seen 15 subjects with

recurrent and disabling episodes of ISP. Ten of themshowed RISP as the main complaint and were included inthis study. Three subjects with severe affective disorderrequiring medical treatment, one subject with advancedsleep phase syndrome, and one subject with alcohol abusewere excluded.RISP is a poorly understood disease and there are only rare

polysomnographic data in this population. Here, we report onclinical and polysomnographic data of the 10 subjects withRISP as the main complaint in order to prove the ICSDcriteria and to describe characteristic patterns of the disease.The polysomnographic data were compared with those ofage- and sex-matched narcoleptic patients and with non-complaining healthy controls.

Materials and methods

Subjects

Ten subjects with RISP were studied (6 females and 4 males,aged 37–60 years, mean age: 49.9 years). Besides theroutine medical history, clinical data were assessed by meansof a structured interview with questions about family history,age at onset of SP, the time of SP occurrence during bedrest,the duration of SP episodes, body position during SP,associated symptoms (e.g. hallucinations, anxiety), potentialafter-effects of SP, the degree of daytime sleepiness, thefrequency of dreaming, medication, and countermeasurestaken. Neurological and physical examinations were per-formed routinely on all patients. Beck’s Depression Inven-tory was used as a screening instrument for affectivedisorders.Ten narcoleptic patients (6 females and 4 males, mean age:

51.5 years, range: 35–61 years) and 10 healthy subjects (5females and 5 males, mean age: 51.5 years, range: 34–70 years) served as reference and control groups for thepolysomnographic data. Current MSLT data were availablefor all RISP patients and for six of the narcoleptic patients. Toobtain equal sample sizes, MSLT data from four additionalnarcoleptic patients were added. The final reference group ofnarcoleptic patients for the MSLT analysis consisted of sevenfemales and three males with a mean age of 50.6 years andan age range between 24 and 61 years.

Epworth Sleepiness Scale (ESS)

Daytime sleepiness was assessed with the Epworth Sleepi-ness Scale (ESS) [15] in all subjects. In the ESS, subjects ratetheir chance of dozing off in eight everyday-life situations. Arating is made for each situation on a four-point scale (0 to 3).Thus the total ESS score varies between 0 and 24. The scorerepresents the summed situational sleep propensity.

Polysomnography

Sleep was polygraphically recorded (polysomnography,PSG) for two consecutive nights between 11 pm and 6 am.

The following sleep biosignals were recorded and digitallystored with a Sagura recording system (SAGURA MedicalSystems Inc., Muhlheim/Main, Germany): EEG from F3-A1,C3-A2, C4-A1, O1-A1, horizontal EOG, chin EMG frommental and submental recording sites, EMG from the tibialisanterior muscle of the left and right leg, ECG, pulseoximetry, respiration (combined mouth and nasal air flow,chest and abdominal belts for respiratory effort). Sleep stageswere visually analysed according to the criteria of Rechts-chaffen and Kales [24].

Multiple Sleep Latency Test (MSLT)

The MSLT was performed between the first and the secondPSG night at 9 am, 11 am, 1 pm, 3 pm and 5 pm. TheMSLT-30 version of the test [12] was used, in which subjectsremain in bed for 30 min during each run, regardless ofwhether or not they fall asleep. For statistical analysis,individual medians were computed for sleep stage 1 and 2latencies, and the number of sleep onset REM phases(SOREMP), defined as an REM latency <15 min, wascounted.

HLA typing

HLA typing was performed for all patients with RISP ornarcolepsy but not for healthy controls.

Statistics

Groups of subjects were compared with the Kruskal–Wallistest, and descriptive post-hoc comparisons were performedwith the Mann–Whitney U-test. Nonparametric tests wereapplied owing to the skewed distribution of different sleepvariables.

Results

Clinical data of RISP patients

Subject BU suffered from drug-treated diabetes and arterialhypertension and showed signs of a generalized polyneur-opathy. None of the other patients showed any deviation onneurological examination. Subject MW had arthrosis andused tramadol as required (approximately 100 mg/week).The subject was asked to stop drug intake for 1 week prior toand during the stay in hospital. Subject ML suffered fromdrug-treated arterial hypertension and coronary heart disease.All other subjects were drug-free.The range of age among RISP patients upon their first

experience of SP varied widely from 15 to 52 years (median:29 years). None of the RISP patients had ever experiencedcataplectic attacks. In the present series of patients, there was

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one familial case of RISP with two afflicted family members(HS, female, and GB, male; table 1). Three subjects withRISP (AW, GB, ML) were HLA DR2(15) positive, while theother seven showed a negative HLA typing. Remarkably, theDR2(15) haplotype was heterogeneous in the familial case.Seven subjects reported that they experienced SP episodes

during spontaneous awakenings in the second half of thenight or at the final awakening in the morning, while twosubjects experienced ISPs exclusively at sleep onset. Twosubjects reported ISP during daytime naps, one of whom(AW) developed ISPs exclusively during daytime naps in a30� to 45� upright position. Overall, the duration of ISPepisodes varied between a few seconds and several minutes.Seven subjects were predominantly in a supine positionduring SP episodes, while one subject tended to experienceSP in a right-leaning body position, and two did notrecognize a systematic relationship between body positionand the occurrence of ISP.While most subjects were not aware of precipitating

factors in the occurrence of SP events, subjects GB and MLreported experiencing SP in association with physical orpsychic stress. Episodes of SP in subject BW were morefrequent after night shifts and able to be provoked by sleepdeficiency. Subjects HS and WM both experienced night-mares of stereotypical frightening character prior to each SPepisode. Besides the inability to move, all subjects experi-enced a state of pronounced fear during ISP with increasedintensity during the course of the SP episode. The state offear was accompanied in four subjects by shortness of breath,in three subjects by palpitation or a sensation of increasedheart rate, and in one subject by a metamorphopsia of thetongue and the right arm. In subject AZ, SP episodes werealways accompanied by acoustic, visual and tactile halluci-nations; in subject WM, exclusively by tactile hallucinationsand sweating. Subject AZ repeatedly saw, heard or felttouched by her deceased mother during SP episodes. The SPepisodes in patient WM were always introduced by a dreamdealing with a frightening childhood event (‘I was knockeddown and saw a trunk falling down from a truck. I couldn’tescape and the trunk rolled over me and remained lying onmy chest’). At this moment the patient always woke upunable to move and with shortness of breath, in a state of SP.At a certain point during an SP episode, subject HS began toscream. Five other patients succeeded in making groaning orhissing noises in order to draw somebody’s attention to theiractual state. These latter subjects reported that being touchedby the bed partner is the most effective procedure toterminate an SP episode. Three of the 10 subjects haddifficulty resuming sleep after an SP episode, and onereported being frightened by the event for several hours orlonger.

Comparison of RISP patients, narcoleptic patientsand healthy controls

The three groups (RISP, NAR, and CON) did not differsignificantly in age (M ± SD; CON: 51.5 ± 9.5, NAR:51.5 ± 10.0, RISP: 48.2 ± 7.7). The groups were alsocomparable in their gender ratio (f/m ratio; CON: 5/5,NAR: 6/4, RISP: 6/4).

Polysomnography

None of the subjects showed signs of periodic limbmovements while sleeping. One RISP patient (BU) had amild obstructive sleep apnoea with a respiratory disturbance

index (RDI) of 12 per hour during night 2 and oxygendesaturation values as low as 85%. PSG results for RISPpatients on both recording nights are summarized in table 2.The groups differed in REM sleep latency (P ¼ 0.008)

and marginally in latency to stage 2 sleep (P ¼ 0.056).Descriptive post-hoc pairwise comparisons of data for night 2showed that sleep latency in RISP patients was longer(40.6 ± 25.3 min) than that in either control subjects(19.2 ± 15.6 min; P ¼ 0.043) or narcoleptic patients(19.5 ± 8.8 min; P ¼ 0.035), whereas the latter two groupsdid not differ. RISP patients also differed from narcolepticpatients in having longer REM sleep latencies (83.2 ±50.7 min vs. 32.1 ± 41.5 min; P ¼ 0.016). As expected,the mean REM sleep latency was shorter in narcolepticpatients than in control subjects (98.7 ± 54.8 min; P ¼0.004), while RISP patients and control subjects did notdiffer in REM sleep latency (P ¼ 0.705).There were no significant group differences in sleep

efficiency (CON: 87.0 ± 6.5%, NAR: 81.2 ± 10.8%, RISP:77.8 ± 12.6%; P ¼ 0.140), in percentage of REM sleep(P ¼ 0.107), or in the proportion of NREM sleep stage 1(CON: 8.0 ± 5.4%, NAR: 12.6 ± 4.8%, RISP: 10.6 ± 5.0%;P ¼ 0.169), stage 2 (CON: 61.8 ± 6.9%, NAR: 58.4 ±7.5%, RISP: 60.6 ± 9.5%; P ¼ 0.736), or the combinedstages 3 and 4 (CON: 9.8 ± 6.5%, NAR: 5.6 ± 6.9%, RISP:10.0 ± 10.5%; P ¼ 0.382). The mean percentage of REMsleep in the RISP patients (18.2 ± 45.8%) was lower but notsignificantly so than that in control subjects (19.5 ± 6.0%)and narcoleptic patients (22.5 ± 3.9%).In RISP patients, sleep efficiency varied between 56.2%

and 94.4% the first night and increased in six subjects thesecond night (range: 58.2% to 94.6%). The median of sleeplatency was 30.25 min on night 1 (range: 5.5 to 91.5 min)and 25.5 min on night 2 (range: 9.0 to 51.0 min), while thelatency of REM sleep varied between 6.5 and 201.0 min onnight 1, and between 26.0 and 117.0 min on night 2.Although REM sleep latency was rather low (<40 min) onboth nights in two RISP patients (GB and ML), only a singleSOREM episode was observed in one patient (ML, night 1).The median of the different sleep stages on night 1 was

12.2% for S1, 60.05% for S2, 7.3% for slow wave sleep(S3 + S4), and 17.25% for REM sleep. On night 2, themedians were 7.4% for S1, 66.4% for S2, 3.1% for slowwave sleep and 17.45% for REM sleep.There were some peculiarities of REM sleep in this group

of RISP patients. Besides occasional shortened REMlatencies in patients GB and ML, the duration of theNREM–REM sleep cycle was unusually short in somesubjects: GB had six NREM–REM cycles on night 1 with anaverage duration of 64.2 min, and five NREM–REM cycleson night 2 with an average duration of 78.1 min. Patient WMhad four NREM–REM cycles on night 1 with an averageduration of 46.5 min, and six NREM–REM cycles on night 2with an average duration of only 37 min. In two othersubjects (AZ and BU), the REM sleep episodes werefrequently interrupted by intrusion of other sleep stages orwakefulness.

MSLT-30

The median of stage 1 sleep latencies was significantly longerfor RISP than for narcoleptic patients (11.5 min, range: 5.5–15.0 min vs. 2.5 min, range: 1.0–23.0 min, respectively;P ¼ 0.003). This was also true for stage 2 latencies(18.5 min, range: 11.5–24.0 min vs. 7.8 min, range: 4.5–24.0 min, respectively; P ¼ 0.023). It should be mentioned

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Table1.Demographicandclinicaldataofpatientswithrecurrentisolatedsleepparalysis(RISP).

Subject

BW

AZ

BU

CS

GB

HS

KK

ML

WM

WT

Gender

MF

FF

MF

FF

Mm

Age(years)

40

58

57

53

54

61

58

38

35

61

Familycase

no

no

no

no

yes

yes

no

no

no

no

HLADR2

(15)typing

positive

negative

negative

negative

positive

negative

negative

positive

negative

negative

AgeatSP

onset(years)

33

48

16

40

14

22

15

25

52

51

Frequencyof

ISPepisodes

1–3/week

1/week

12/year

6/year

12/year

8–12/year

10–12/year

1–3/month

1/week

12/year

TimeofISP

occurrence

duringsleep

daytimenaps

2ndhalfof

nightoratfinal

awakening

2ndhalfof

nightor

atfinal

awakening

sleeponset

sleeponset,

daytimenaps

2ndhalfof

nightorat

finalawakening

2ndhalfof

nightorat

final

awakening

2ndhalfof

nightorat

finalawakening,

rarelyat

sleeponset

2ndhalfof

nightorat

finalawakening

2ndhalfof

nightorat

finalawakening

Durationof

ISPepisodes

secondsup

toseveral

minutes

secondsup

to8min

secondsupto

severalminutessecondsupto

several

minutes

seconds

upto3min

seconds

upto10min

seconds

upto3min

seconds

uptoseveral

minutes

secondsupto

several

minutes

secondsupto

several

minutes

Bodyposition

during

ISPepisode

supine,

30–45�

upright

rightside

notspecific

supine

predominantly

supine

predominantly

supine

exclusively

supine

notspecific

predominantly

supine

predominantly

supine

Accompanying

symptoms

besidesfear

tachycardia

visual,acoustic

andtactile

hallucinations

metamorphopsia

ofthetongue

andrightarm

shortnessof

breath

palpitation

andtachycardia

shortnessof

breath,

preceding

nightmare

no

shortnessof

breath,fear

ofsmothering

palpitation,

sweating,

tactile

hallucination

no

Abilitytofall

asleep

afterISP

easy

easy

difficult

prolonged,

upto2h

easy

prolonged,

upto2h

easy

easy

unablefor1h

easy

Predictorsof

ISPevents

nightshift,

sleep

deficiency

none

none

none

preceding

physical/psychic

distress

none

none

preceding

psychic

distress

none

none

Dreams

raredreams,

normalqualitynormalquality,

nightmares

twiceaweek

frequentdreams,

normalquality

raredreams,

normal

quality

raredreams,

normal

quality

nightmaresonly

inassociation

withISP

raredreams,

normalquality

raredreams,

normal

quality

frequent

nightmares,

stereotypical

dream

priortoSP

raredreams,

normalquality

Strategiesto

overcome

ISP

none

none

none

groaning,

beingtouched

bythebed

partnermay

finishanSP

groaning,inthe

beginningof

SPdeep

breathing

screaming,

beingtouched

bythebed

partnermay

finishanSP

groaning,being

touchedbythe

bedpartner

mayfinishanSP

hissing,

beingtouched

bythebed

partnermay

finishanSP

groaning,

beingtouched

bythebed

partnermay

finishanSP

none

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that individual medians of stage 2 latencies were computedfor eight narcoleptic patients only, because two patientsentered stage 2 only in two of the five MSLT sessions andthus were excluded from stage 2 analysis. The two patientgroups also differed clearly in the number of SOREMPs.While all narcoleptic patients had SOREMPs, rangingbetween three and five per patient, such events wereextremely rare in patients with RISP. SOREMPs occurredonly in two out of ten patients with RISP, with a frequency ofone and two, respectively. Thus, the propensity for REMsleep throughout the day was much higher in narcolepticpatients than in RISP patients.

Epworth Sleepiness Scale (ESS)

The groups differed in the degree of sleepiness, measured bythe ESS. The mean ESS score was lowest in the controlgroup (6.0 ± 3.5; Md ¼ 6.5, range: 1–11), slightly higher inRISP patients (8.6 ± 5.4; Md ¼ 9.0, range: 2–20) andsignificantly higher in narcoleptic patients (19.1 ± 4.1;Md ¼ 20.5, range: 11–23). Groups differed significantly(P ¼ 0.000) in the Kruskal–Wallis test. Post-hoc Mann–Whitney U-tests confirmed that narcoleptic patients differedfrom healthy controls (P ¼ 0.000) and from RISP patients(P ¼ 0.001), while the latter two groups did not differ. Allnarcoleptic patients had an ESS score of 11 or greater, whilewithin the control group there was only one subject with ascore above 10 (ESS 11) and only two RISP patients scoredhigher than 10 (ESS 14 and 20). The data show that increasedsleepiness was rare in the group of RISP patients.

HLA DR2

While all narcoleptic patients were positive for HLADR2(15), this was true for only three patients with RISP.Interestingly, there was HLA DR2(15) heterogeneity in thefamily case of GB and HS.

Discussion

The PSG data suggest different triggering mechanisms insleep paralysis and cataplexy. RISP patients displayed normalor sometimes prolonged sleep latencies, and most REMlatencies were normal. Only one single SOREM episode wasseen during night sleep and two SOREM episodes (latency<20 min) in the MSLT-30. Finally, RISP patients had moredifficulty falling asleep than healthy control subjects.Certain peculiarities of REM sleep were seen, which may

in some way be conducive to the occurrence of ISP.Specifically, five out of 20 (25%) REM sleep latencies wereshort (<60 min), two subjects displayed remarkably shortNREM–REM sleep cycles, and there was a pronouncedfragmentation of REM sleep in two other subjects.Additionally, the mean percentage of REM sleep was ratherlow for this age group, while the percentage of slow wavesleep was rather high. While the immediate transition fromwakefulness to REM sleep seems to be a pathophysiologicalprerequisite for cataplexy, the instability of REM sleep maybe the clue to understanding the pathophysiology of SP. Thisassumption needs further testing by means of a systematicanalysis of the microstructure of sleep in RISP patients.The observation that SP episodes can be provoked by a

disturbance of the sleep–wake cycle, jet lag, sleep disruption,or non-restorative sleep also suggests that fragmentation ofsleep, or REM sleep, may be a critical factor in theoccurrence of SP [9,10,25–27].T

able2.Sleepparametersonnight1(N1)andnight2(N2)ofpatientswithRISP.

Subj

SEI(%)

SOL(S2)

REM-Lat

%S1

%S2

%SWS

%SREM

N1

N2

N1

N2

N1

N2

N1

N2

N1

N2

N1

N2

N1

N2

BW

77.1

84.0

40.0

31.0

79.5

61.0

1.6

3.0

69.2

74.5

1.4

1.6

26.6

19.7

AZ

77.8

74.8

71.5

25.5

69.5

74.0

15.5

18.5

52.9

62.6

14.2

1.9

17.4

15.0

BU

82.6

84.1

26.5

15.0

71.5

50.5

12.8

15.5

48.0

44.7

27.0

25.8

10.9

12.6

CS

56.2

76.1

36.5

38

78.5

86.0

14.4

7.2

70.4

70.2

00

14.6

22.4

GB

85.3

93.7

30.0

20.5

37.0

32.0

11.6

5.8

73.3

71.4

2.0

3.7

12.5

18.5

HS

69.5

71.3

54.0

51.0

201.0

117.0

16.5

12.6

48.0

44.6

19.4

25.5

15.3

16.4

KK

94.4

91.2

5.5

9.0

105.0

61.5

6.0

6.7

60.9

67.8

12.6

2.5

20.2

22.9

ML

60.4

58.2

91.5

29.5

6.5

26.0

13.6

7.7

68.1

65.1

0.5

13.5

17.8

13.1

WT

82.6

94.6

26.0

12.0

104.0

111.5

5.1

5.8

54.1

48.4

23.0

29.4

17.1

15.6

WM

92.3

86.0

24.0

25.5

79.5

56.5

8.6

7.6

61.2

67.7

00

29.1

24.3

Mean±SD

77.8±12.6

81.4±11.4

40.6±25.3

25.7±12.7

83.2±50.7

67.6±30.3

10.6±5.0

9.0±4.9

60.6±9.5

61.7±11.4

10.0±10.5

10.4±12.1

18.2±5.8

18.1±4.2

REM-Lat,REMsleeplatency,SEI,sleepefficiency,SOL,sleeponsetlatency(S2),Subj.,subject,SWS,slowwavesleep(S3+S4)

6 Bjorn W. Walther and Hartmut Schulz

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Since we were not successful in recording an SP episodeduring night sleep in the present series of sleep polygraphies,the question of the relationship between REM sleep and SP isstill unsolved. SP remains an elusive symptom, difficult tocapture under sleep laboratory conditions. Thus, homerecordings over a longer period of time may be a prerequisitefor the recording of acute episodes of SP in patients withRISP.The ICSD [14] recommends the occurrence of SOREM

episodes as a diagnostic criterion for RISP, although,according to our knowledge, there are no other polysom-nographic studies with RISP patients. The assumption ofthe occurrence of SOREMPs in ISP gets some support inthe results of Takeuchi et al. [26,27]. These authors elicitedSP by sleep interruption in normal subjects, and suggestthat the occurrence of SP episodes is facilitated bySOREMPs. However, the trigger mechanisms in ISP andcataplexy seem to be different, and the direct transitionfrom wake to REM sleep seems to be an insufficientpathophysiological explanation for the occurrence of ISP.Although one of our patients did show a SOREM episodeon one night, the PSG data in general suggest thatSOREMPs are not typical for patients with RISP. SPattacks seem to represent a dissociative state, wheredifferent physiological (muscle atony) and mental events(hallucinations) are extricated from their normal bindingwith the behavioural state of REM sleep.In contrast to the patients of Dahlitz and Parkes [6],

daytime sleepiness was not increased in most of our patients.The reason for this difference is unclear and may be due todifferences in the recruitment procedure of RISP patients. Inany case, severe daytime sleepiness does not seem to be aprerequisite for diagnosing RISP.The phenomenology of ISP-associated experiences dif-

fered widely between subjects. They reported variousaccompanying symptoms besides fear and shortness ofbreath. Only one subject had visual, auditory, and tactilehallucinations in association with SP episodes; one othersubject had only tactile hallucinations concomitantly. Oneother subject experienced somatagnostic phenomena, such asa disturbance of the body image with metamorphopsia of thetongue and the right arm. The systematic interviews showedthat most ISP events occurred while subjects were in a supinebody position; only subject AZ experienced most of her ISPepisodes in the right side position. These data stronglysupport the recent findings of Cheyne [4] and Dahmen et al.[7]. These authors additionally report on a close relationshipbetween the occurrence of ISP and the supine position.An ISP episode normally lasts seconds up to several

minutes and generally terminates spontaneously. Six patientsdeveloped a strategy to overcome ISP by producing noises,which allowed the bed partner to interrupt the episode bytouching the subject. These data confirm the recentlypublished results from a web survey [3].Finally, it should be pointed out that four of the 10 subjects

presented a late onset form of sleep paralysis, with the firstsymptoms occurring at the age of 40, 48, 51 and 52 years,respectively. In this connection, it is interesting to note thatWing et al. [29] described recently a bimodal distribution ofISP onset with a first peak at adolescence and a second oneabove 60 years. In the Dahlitz and Parkes’ sample of subjectswith ISP, the median age at the first occurrence of ISP was16 years (range: 5 to 35 years) [6].The present results support the diagnostic conceptualization

of RISP as a separate disease. In contrast to the establishedclose association between HLA DR2(15) and narcolepsy–

cataplexy, the prevalence of HLA DR2(15) in RISP patientsseems to be comparable to that in the general population[1,17]. The rate was 3/10 (33%) in the present sample and 4/22(18.2%) in the study of Dahlitz and Parkes [6].The three HLA DR2(15)-positive RISP patients showed

some peculiarities in comparison with the HLA DR2(15)-negative patients. According to anamnestic data, twodisplayed SP either during daytime naps or at sleep onset.Two of the three patients showed short REM latencies, andout of all the RISP patients, only one had a single SOREMPon night 1. None of the three patients showed SOREMPs ornotably short latencies for S1 or S2 in the MSLT-30, and twopatients did not sleep at all during the five MSLT sessions.The ESS values for all three patients also revealed noincreased daytime sleepiness.From a clinical point of view, RISP may fulfil the criteria

for a disease under the following conditions. First, the SPepisodes occur repeatedly; second, the episodes are experi-enced as frightening; and third, the subject has no effectivecountermeasures at his or her disposal to end the SP episode.In our sample, nine out of 10 subjects came to the outpatientsleep clinic seeking help. Only one patient had additionally amild form of sleep apnoea, while in all other cases noaccompanying sleep disorders were seen.

Acknowledgements

We are grateful to Corinna Schneider, Barbel Rothe, JannynDoring, Birgit Schubert, Diana Wickner for their help incollecting the data, and Catherine Oliver for criticallyreading the manuscript.

References

[1] Aldrich MS: Narcolepsy. New Engl J Med: 323, 389–394, 1990.

[2] Bell CC, Shakoor B, Thompson B, Dew D, et al.: Prevalence ofisolated sleep paralysis in black subjects. J Natl Med Assoc 81:805–808, 1989.

[3] Buzzi G, Cirignotta F: Isolated sleep paralysis: a Web survey.Sleep Res Online 3: 61–66, 2000.

[4] Cheyne JA: Situational factors affecting sleep paralysis andassociated hallucinations: position and timing effects. J SleepRes 11: 169–177, 2002.

[5] Cheyne JA, Newby-Clark IR, Rueffer SD: Relations amonghypnagogic and hypnopompic experiences associated with sleepparalysis. J Sleep Res 8: 313–317, 1999.

[6] Dahlitz M, Parkes JD: Sleep paralysis. Lancet 341: 406–407,1993.

[7] Dahmen N, Kasten M, Mueller MJ, Mittag K: Frequency anddependence on body posture of hallucinations and sleepparalysis in a community sample. J Sleep Res 11: 179–180,2002.

[8] Everett HC: Sleep paralysis in medical students. J Nerv MentDis 3: 283–287, 1963.

[9] Folkard S, Condon R, Herbert M: Night shift paralysis.Experientia 40: 510–512, 1984.

[10] Fukuda K: Sleep paralysis and sleep onset REM period in nor-mal individuals. In: Ogilvie, RD and Harsh, JR (eds): Sleeponset mechanisms: normal and abnormal processes. AmericanPsychological Association, Washington DC, pp. 161–181, 1994.

[11] Fukuda K, Miyasita A, Inugami M, Ishihara K: High prevalenceof isolated sleep paralysis: Kanashibari phenomenon in Japan.Sleep 10: 279–286, 1987.

[12] Geisler P, Cronlein T, Tracik F, Zulley J: The MSLT-30: an‘easy-to-use’ variant of the MSLT with improved diagnosticvalue. J Sleep Res 7: 100, 1998.

[13] Hishikawa Y, Shimizu T: Physiology of REM sleep, cataplexy,and sleep paralysis. Adv Neurol 67: 245–271, 1995.

7

Somnologie 8: 1–9, 2003

UN

CO

RR

EC

TED

PR

OO

F

[14] [ICSD]. International classification of sleep disorders, revised:Diagnostic and coding manual. American Sleep DisordersAssociation, Rochester, MN, 1997.

[15] Johns MW: A new method for measuring daytime sleepiness:the Epworth Sleepiness Scale. Sleep 14: 540–545, 1991.

[16] Kleßmann E: Die Mendelssohns. Bilder aus einer deutschenFamilie [The Mendelssohns. Pictures from a German Family].Insel, Frankfurt/Main, pp. 41–42, 1993.

[17] Neely S, Rosenberg R, Spire JP, Antel J et al.: HLA antigens innarcolepsy. Neurology 37: 1858–1860, 1987.

[18] Ness RC: The old hag phenomenon as sleep paralysis: a bio-cultural interpretation. Culture Med Psych 2: 15–39, 1978.

[19] Ohaeri JU, Odejide AO, Ikuesan BA, Adeyemi JD: The patternsof isolated sleep paralysis among Nigerian medical students.J Natl Med Assoc 81: 808–810, 1989.

[20] Ohaeri JU, Odejide AO, Ikuesan BA, Adeyemi JD: The patternsof isolated sleep paralysis among Nigerian nursing students.J Natl Med Assoc 84: 67–70, 1992.

[21] Ohayon MM, Zulley J, Guilleminault C, Smirne S: Prevalenceand pathologic associations of sleep paralysis in the generalpopulation. Neurology 52: 1194, 1999.

[22] Paradis CM, Friedmann S, Hatch M: Isolated sleep paralysisin African Americans with panic disorders. Cult Divers MentHealth 3: 69–76, 1997.

[23] Penn NE, Kripke DF, Scharff J: Sleep paralysis among medicalstudents. J Psychol 107: 247–252, 1981.

[24] Rechtschaffen A, Kales A: A manual of standardized termin-ology, technique and scoring system for sleep stages of human

subjects. Brain Information Service, National Institutes ofHealth, 1968.

[25] Snyder S: Isolated sleep paralysis after rapid time zone change(jet lag) syndrome. Chronobiologia 10: 377–379, 1983.

[26] Takeuchi T, Fukada K, Saski Y, Inugami M, Murphy TI: Factorsrelated to the occurrence of isolated sleep paralysis elicitedduring a multi-phasic sleep–wake schedule. Sleep 125: 89–96,2002.

[27] Takeuchi T, Miyasita A, Sasaki Y, Inugami M, Fukuda K: Iso-lated sleep paralysis elicited by sleep interruption. Sleep 15:217–225, 1992.

[28] Waller JA: A treatise on the incubus, or nightmare, disturbedsleep, terrific dreams, and nocturnal visions; with the means ofremoving these distressing complaints. Cox, London, 1816.[Johann Waller: Abhandlung von dem Alpdrucken, dem gest-orten Schlafe, erschreckenden Traumen und nachtlichenErscheinungen. Nebst der Heilart dieser Zufalle. German editionand translation by Elias Wolf. Philipp Heinrich Guilhaum,Frankfurt/Main, 1820].

[29] Wing YK, Chiu H, Leung T, Ng J: Sleep paralysis in the elderly.J Sleep Res 8: 151–155, 1999.

[30] Wing YK, Lee ST, Chen CN: Sleep paralysis in Chinese: ghostoppression phenomenon in Hong Kong. Sleep 17: 609–613,1994.

[31] Yoss RE, Daly DD: Criteria for the diagnosis of the narcolepticsyndrome. Proc Mayo Clin 32: 320–328, 1957.

8 Bjorn W. Walther and Hartmut Schulz

Somnologie 8: 1–9, 2004

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