Isolated Cataplexy: a Familial Study

Henry Ford Hospital Medical Journal

Volume 36 Number 1 Article 7

12-1988

Isolated Cataplexy: A Familial Study

Kristyna M. Hartse

Frank J. Zorick

Jeanne M. Sicklesteel

Thomas Roth

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Recommended Citation Hartse, Kristyna M.; Zorick, Frank J.; Sicklesteel, Jeanne M.; and Roth, Thomas (1988) "Isolated Cataplexy: A Familial Study," Henry Ford Hospital Medical Journal : Vol. 36 : No. 1 , 24-27. Available at: https://scholarlycommons.henryford.com/hfhmedjournal/vol36/iss1/7

This Article is brought to you for free and open access by Henry Ford Health System Scholarly Commons. It has been accepted for inclusion in Henry Ford Hospital Medical Journal by an authorized editor of Henry Ford Health System Scholarly Commons. Isolated Cataplexy: A Familial Study

Kristyna M. Hartse, PhD,* Frank J. Zorick, MD,^ Jeanne M. Sicklesteel, BA,t and Thomas Roth, PhD+

Four members of a family, a mother, her two sons, and the mother's second cousin, presented with a history of isolated cataplexy withoul excessive daytime sleepiness or other symptoms typical of narcolepsy. They were polygraphically monitored during one night followed by a day of multiple nap tests. No subjecl manifested objective daytime sleepiness as measured by .short latencies to sleep onset during daytime naps, and no subjecl exhibited periods of sleep onset rapid eye movement sleep in either the night or nap recordings. The incidence of isolated cataplexy in this family was traced by history through six generations. We conclude lhal isolated cataplexy in this family is a genetically transmilted dominant trait with incomplete penetrance which occurs independently of daytime sleepiness and the full-blown narcolepsy syndrome. (Henry Ford Hosp Med J 1988:36:24-7)

arcolepsy is a disorder of excessive daytime sleepiness fact have narcolepsy will not have SOREM at night. A more N (EDS) which may be associated with symptoms of cata­ rigorous test to determine that individuals with isolated cata­ plexy, sleep paralysis, and hypnagogic hallucinations (1). Al­ plexy do not have undetected narcolepsy would be the demon­ though sleep paralysis and hypnagogic hallucinations can occur stration that polygraphically defined EDS and SOREM periods as benign events in normal subjects (2), cataplexy, the complete during daytime naps are absent. or partial loss of skeletal muscle tone occurring in response to In this study we used nighttime recordings and daytime nap strong emotional stimuli during waking, is a symptom unique to tests to evaluate four members of a family—a mother, her two narcolepsy. Polysomnographic recordings, however, are essen­ sons, and the mother's second cousin—who are affected with tial for the unequivocal diagnosis of narcolepsy. The distinctive isolated cataplexy and who did not present with any other known electrophysiological feature of narcolepsy is the presence of symptom of narcolepsy. The high familial incidence of this un­ sleep onset rapid eye movement (SOREM) periods (3). SOREM usual phenomenon, which is known in the family as "kinking," periods, like the rapid eye movement (REM) periods that occur has been extensively documented by family members, thus at regular intervals throughout the night, are characterized by allowing the history of "kinking" to be traced through several rapid eye movements, chin muscle atonia, and a low-amplitude generations. EEG similar to that of wakefulness. In contrast to normal sub­ jects who have 90 to 100 minutes of non-REM sleep prior to the first REM period of the night, the narcoleptic typically will make the transition between wakefulness and REM sleep with Methods less than 15 minutes of intervening non-REM sleep. In com­ Subjects parison to normal subjects, daytime nap recordings of narcolep­ The mother, a healthy, white, 27-year-old, has had recurring tic patients reveal the presence not only of rapid latencies to episodes of bodily muscle weakness lasting approximately 5 to sleep onset but also of SOREM periods in daytime naps (1,4,5). 30 seconds since age 8 months. As a baby, the episodes were induced by tickling; as a child and teenager, they were always The appearance of isolated cataplexy in the absence of typical precipitated by laughter. Fear, anger, excitement, or surprise narcolepsy symptoms, particularly EDS, is extremely rare. Gelardi and Brown (6) and Vela Bueno et al (7) have presented have never precipitated an attack. She describes herself during evidence for isolated cataplexy in several members of two differ­ these attacks as being awake and aware of her sum^undings but ent families. Roth (8) has also observed two cases of isolated "floating" and unable to move. The ease with which cataplexy cataplexy. None of these individuals complained of EDS. A sin­ can be induced has decreased with age such that laughter-in­ gle night of polysomnographic recording failed to reveal the duced cataplexy now occurs only when she is fatigued. She has presence of SOREM in individuals affected only with isolated cataplexy. However, in none of these studies was daytime som­ nolence evaluated with multiple nap tests. The conclusion that Submitted for publication: October 20. 1987. narcolepsy was absent in these individuals cannot be confidently Accepted for publication: April 14, 1988. * Fomierly Sleep Disorders Center Henry Ford Hospital. Currently Sleep Disorders Cen­ made solely on the basis of this single recording. Only 44% to ter, St Louis University Hospitals. St Louis. MO. 49% of narcoleptic patients reportedly have SOREM at night tSleep Disorders Center. Henry Ford Hospital. Address correspcmdence to Dr Hartse, Sleep Disorders Center St Louis University Hos­ (9-11). Thus, a strong possibility exists that a subject who may in pitals, 1221 S Grand, St Louis, MO 63104,

24 Henry Ford Hosp Med J—Vol 36, No 1, 1988 Isolated Cataplexy—Hartse et al no history of daytime sleepiness, disturbed nocturnal sleep, Table sleep apnea, hypnagogic hallucinations, or sleep paralysis. Summary of Daytime Nap Recordings Both children, aged 5 Vi and 2 Vi, exhibit brief cataplectic epi­ sodes with laughter or tickling. The older child first experienced Latency to Latency to Latency to Naps* Stage 1 (min) Stage 2 (min)t REM (min)t cataplexy at age 3 months, and the younger child manifested cat­ Nap 1 aplectic attacks at age 8 months. Like their mother, cataplexy is A 26.5 35,0 — induced only by laughter or tickling. Both children are normal in B no sleep no sleep no sleep their physical, intellectual, and emotional development. Neither C 3.0 6,5 — D 11.0 — child is considered excessively sleepy during the day. Mean latency 17.6 ±11.1 22,4 ± 11,1 — In addition to these subjects, a second cousin of the mother on her father's side, who resides in Los Angeles, CA, agreed to par­ Nap 2 A no sleep no sleep no sleep ticipate in the study. This 27-year-old woman has experienced B 21.0 26.0 episodes of cataplexy since age 2 or 3; her cataplexy is also in­ C 10.0 — duced only by laughter. The episodes last for 10 to 15 seconds, D 20.5 26.0 Mean latency 20.4 ± 7.1 28.0 ± 2.0 — end spontaneously, have decreased in frequency with age, and occur now only when she is fatigued. She also has no history of Nap 3 daytime sleepiness, disturbed nocturnal sleep, sleep apnea, A 23.0 32.0 H no sleep no sleep no sleep sleep paralysis, or hypnagogic hallucinations. C 10.5 11.0 D 18.5 26.0 Polysomnographic recording Mean latency 20.5 ± 7.1 24.8 ± 8.2 — The mother and her youngest son were monitored for one Nap 4 night using standard techniques for continuous recording of the A 7.0 — B central and occipital EEG, chin muscle activity, and eye move­ no sleep no sleep no sleep C 14.0 — ments. The mother's cousin was monitored at the Holy Cross D 21.0 Hospital Sleep Disorders Center in Mission Hills, CA, using Mean latency 18.0 ± 8.5 — — identical procedures. On the day following the all-night record­ Grand Mean 19.1 ± 8.7 27.0 ± 7.3 ing, the Multiple Sleep Latency Test (MSLT) was conducted in *A = the mother. B = the older son, C = the younger son. and D - the mother s all three subjects using an identical protocol. At 10 AM, 12 PM, second cousin. ' The dash indicates that this sleep stage did not occur 2 PM, and 4 PM, the subjects were instmcted to lie down in a Note; If the subject did not reach stage 1 or 2. the latency to either stage was assigned quiet, dark room and to try and fall asleep. If sleep did not occur the value ofthe numberof minutes in bed in calculating the mean. within 30 minutes, the nap was terminated. If stage I or REM sleep occurred within the 30-minute period, the nap was termi­ nated 15 minutes after the first epoch of either stage. The max­ cousin. The latencies to REM sleep at night were 182.5 minutes, imum length of time in bed per nap was 45 minutes. Subjects 250.5 minutes, and 59.5 minutes in each subject, respectively. were cautioned to remain awake between naps and were ob­ In fact, with the exception of the cousin, these REM latencies served by technicians to assure that sleep did not occur. were somewhat increased compared to normal subjects (13). Al­ The older son did not have a nighttime polysomnographic re­ though the cousin's latency was somewhat decreased compared cording performed, but the daytime MSLT was performed at a to normal subjects, it was not within the range of that reported in later date. His mother reported that his nighttime sleep at home narcoleptics. No subject exhibited evidence prior to the first before the MSLT was the same as usual. She remained with her REM period for stage 7 sleep (14), which has been described as son during the day of nap testing. the displacement of REM sleep variables, such as rapid eye All recordings were scored for sleep stages according to stan­ movements or chin muscle atonia, into the non-REM sleep dard criteria (12). Stage 1 sleep onset latency in daytime naps stages. In summary, no polygraphic evidence in the nighttime was determined by the disappearance of waking alpha activity recordings suggested the presence of SOREM or a diagnosis for greater than 50% of the 30-second epoch. Videotape record­ of narcolepsy. ings were made in conjunction with simultaneous polygraphic The daytime nap recordings confirmed the absence of monitoring during cataplectic attacks in both children. SOREM periods as well as the absence of sleepiness in all four subjects (Table). Inspection of the recordings revealed no evi­ Family history dence for stage 7 sleep in the mother's or her cousin's naps. However, the 10 AM nap of the younger son showed five periods The cataplexy which these four subjects experience also oc­ lasting 3 to 6 seconds in which eye movements were associated curs in many other members of their family. Through corre­ with decreased, but not absent, chin muscle tonus and K-com- spondence with older family members, the mother has traced plexes typical of stage 2 sleep. These brief, REM-like episodes "kinking" through several generations of her family tree. meet the criteria for stage 7 sleep. The shortest latencies to stages 1 and 2 also occurred in this nap. No evidence for stage 7 Results sleep was present in any other nap of the younger son. Two 10- to The nighttime polysomnographic recordings showed no evi­ 15-second episodes occurred in the older child's 12 PM nap dence for SOREM periods in the mother, her younger son, or her which were interpreted as possible stage 7 sleep. However,

Henry Ford Hosp Med J—Vol 36. No 1, 1988 Isolated Cataplexy—Hartse el ai 25 L n mn IT t

Figure—The family tree: o = unaffected females: O fw/?/! numbers) = number of unaffected females: • = females affected with isolated cataplexy; o = unaffected males; o (with numbers) = number of unaffected males; ^ = tnales affected with isolated cata­ plexy; O (with number) = number of persons of unknown sex or history; large hatched circle = the mother in this report; large hatched squares = her two sons; and the arrow indicates the mother's cousin.

no stage 7 sleep or clear SOREM occurred in any other nap of her sisters (generation V) are affected. Our subject's cousin is this subject. also the only sibling in her family who is affected, but her No evidence was present in any subject for pathological mother is affected. Both males and females in the family are af­ daytime sleepiness as demonstrated by rapid sleep onset laten­ fected, although females are more often affected than males. Of cies in daytime naps. The mean latency to stage I sleep across all generarion I's offspring, 42% (24/57) of females and 27% subjects ranged between 17.6 ±11.1 minutes (nap 1) to 20.5 ± (14/52) of males are affected; 35% (38/109) ofall descendants 7.1 minutes (nap 3). Only in the first nap of the younger son and are affected, suggesting that isolated cataplexy in this family is a in the last nap of his mother did the latency to stage 1 approach dominant trait with incomplete penetrance. In every family that latencies of 5 minutes or less previously reported in narcoleptic has an affected male or female parent, at least one offspring is patients (4,5,15). In the younger son, three of four stage I laten­ affected. The two exceptions are an affected female in genera­ cies were 10 minutes or longer; in the older son, no sleep oc­ tion IV and an affected male in generation III who produced no curred in three of four naps; in the mother, three of four stage 1 affected male or female offspring. Conversely, it is apparently latencies were 10 minutes or longer; and in the mother's cousin, not necessary for a parent to be affected in order to produce four of four stage 1 latencies were longer than 10 minutes. The affected offspring. In the direct line of descent of the mother grand mean to stage 1 sleep onset across all subjects and all naps and her two sons, neither her father or his brother are affected, was 19.1 ± 8.7 minutes. Thus, no convincing evidence was yet each of these men has a single affected female offspring present in the MSLT for either the presence of SOREM periods who in tum produced affected offspring. Although not entirely or EDS in any of the four subjects. reliable by history, no reports document any symptoms of EDS in this family. In both children, cataplectic attacks were induced by their mother tickling them. The attacks lasted from 1 or 2 to 20 sec­ onds and were characterized by brief drooping of the head in the Discussion shortest attacks to complete flacidity of the entire body during The major conclusions of this study are that isolated cataplexy the longest attacks. Spontaneous recovery of muscle tonus was can occur independently of EDS or the other symptoms of nar­ rapid and took from less than 1 to about 5 seconds. Polygraphic colepsy and can be genetically transmitted through successive recordings confirmed the absence of muscle tonus during the at­ generations. Several lines of evidence support these conclu­ tacks. Excessive movement artifact, however, obscured the sions. First, the onset of cataplectic attacks began in all four of EEG. Neither child appeared to experience any discomfort or our subjects earlier than age 3. Very early age of onset is atypical anxiety as the result of the episodes. Although the younger child of narcolepsy. The peak onset age of daytime somnolence and was crying and fearful upon first arriving in the Sleep Disorders cataplectic attacks in surveys of large narcoleptic populations Center, he did not experience any muscle weakness charac­ has been reported to range from about 12 to 20 years (16-19). All teristic of cataplexy. the subjects in our study showed signs of cataplexy at a much The incidence of cataplexy in this family is shown in the Fig­ younger age. Similarly, the family with isolated cataplexy de­ ure. In the direct line of descent of the children and their mother, scribed by Vela Bueno et al (7) exhibited an onset age of it is not certain whether the mother's great-great-grandfather 3 months. In a second study of isolated familial cataplexy, the (generation I) experienced "kinking." However, the brother of age of onset was somewhat later, between 5 to 10 years (6), but her great-great-grandfather had cataplexy which was present in this is still younger than the typical age reported for narcolep­ his succeeding generations, indicating that one parent of genera­ tics. Second, none of our subjects showed SOREM charac­ tion I probably had cataplexy. The familial history of other teristic of narcolepsy. Although both children exhibited some members of generation I is unknown. Both the mother's great- brief, ambiguous periods which may be interpreted as stage 7 grandmother (generation II) and grandmother (generation III) sleep, this finding does not support a diagnosis of narcolepsy. were affected. Neither our subject's father (generation IV) nor Both Maron et al (20) and Karacan et al (21) have observed REM

26 Henry Ford Hosp Med J—Vol 36. No 1, 1988 Isolated Cataplexy—Hart.sc et al sleep in the daytime naps of some normal subjects. We also have 6. Gelardi JM, Brown JW. Hereditary cataplexy. J Neurol Neurosurg Psychi­ found that some normal subjects exhibit REM onsets during atry 1967;30:455-7. MSLT moming naps (9). It is important to reemphasize that nei­ 7. Vela Bueno A, Campos Castello J, Jimenez Baos R. Hereditary cataplexy: Is it primary cataplexy? Waking and Sleeping 1978;2:125-6. ther child exhibited full-blown SOREM periods characteristic of 8. Roth B. Narcolepsy and hypersomnia. In: Williams RL, Karacan I, eds. the narcoleptic. Third, none of our subjects showed evidence of Sleep disorders: Diagnosis and treatment. New York: John Wiley, 1978:29-59. pathological sleepiness as measured by an increased tendency to 9. Hartse KM, Roth T, Zorick F, Moyles T. REM sleep episodes during multi­ fall asleep during daytime naps. 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