Myoclonus

in Familial Restless

Dan

Legs Syndrome

Boghen, MD, FRCP(C), Jean-Marie Peyronnard, MD, FRCP(C)

family were affected over a span of five generations with the restless legs syndrome, trans\s=b\ Eighteen members of a

autosomal dominant trait. patients had myoclonus. The propositus, a 57-year-old man, suffered from repeated, intense, asymmetric flexion jerks of the lower extremities, alternating with fidgeting and friction movements of the legs; all occurred at night prior to sleep and severely interfering with it. The patient's movements ceased with the onset of stage 1 sleep, while in his brother, the motor activity persisted in stages 1 and 2 of sleep. (Arch Neurol 33:368-370, 1976) mitted Ten

as an

legs syndrome consists of deep, ill-defined, disagreeable sensations in the legs and an irresis¬

The

restless

them. The symp¬ toms appear at rest, and mostly in the evening. Temporary relief may be obtained by standing up and walking. Severe insomnia may be a prominent

tible urge to

move

complaint.1

While the familial incidence of the syndrome has been mentioned,13 neiAccepted

for

publication Sept 1, 1975. From the Neurology Section, Department of Medicine, H\l=o^\tel-DieuHospital, and the University of Montreal. Read in part before the 27th annual meeting of the American Academy of Neurology, Miami, 1975.

Reprint requests to H\l=o^\tel-DieuHospital, 3840 St Urbain St, Montreal, Quebec, Canada H2W 1T8 (Dr Boghen).

hereditary character nor the frequent prominence of myoclonus has been emphasized. ther its

REPORT OF CASES

following neurologic examinations were performed: complete blood cell count, skull roentgenogram, electroencephalo¬ gram, electromyogram (EMG), nerve con¬ dition, and chromosome studies. All results The

within normal limits. The following drugs were ineffective in

were

The family pedigree (Figure) shows 18 affected members belonging to five differ¬ ent generations. Personal interviews were conducted with 15 members. Two of the remaining three have died and the third is

only 6-years-old. Case 1.—The

*'

propositus,

man, consulted with

a

57-year-old

in November 1973 because of involuntary jerks of the lower extremities that prevented him from falling asleep at night, and awakened him after the onset of sleep. To obtain relief, he would get up and walk around for approxi¬ mately ten minutes. Following this, he would be comfortable for 20 minutes or so, after which the symptoms would recur. The same movements occasionally occurred during the day when he was sitting or going for a drive, and were aggravated by fatigue. The movements never occurred while he was standing. He denied sensory symptoms. The condition began with excessive restlessness in classrooms when he was 7 years old and has since varied in intensity. Symptoms had become more severe in the preceding year following a bilateral iliac endarterectomy for intermit¬ tent claudication. He was now unable to obtain uninterrupted sleep until 5 am. Once firmly asleep, he continued in this state until 10 am. Because of the increased severity of his illness, he left the job he had had for 20 years and sought alternate

employment.

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us

therapeutic dosage: diazepam, phenytoin sodium, carbamazepine, and methysergide maléate.

Polygraphie recordings on

were

performed

two occasions. Horizontal eye

move¬

ments, EEG, and EMG (with surface elec¬

trodes) of the chin, left tibialis anterior, and gastrocnemius muscles were moni¬ tored on an eight-channel electroencephalograph. The sleep stages were classified according to the criteria of Dement and Kleitmann.4

Sleep deprivation until 6 am helped the patient to fall asleep. Clinical observation showed two types of abnormal motor activity of the legs during the relaxation period preceding sleep. One type consisted of abrupt asymmetric myoclonic jerks ranging from a brisk dorsiflexion of the foot to a triple flexion of the limb, which resembled a withdrawal reflex. These were vigorous, often accompanied by contrac¬ tion of the abdominal muscles and an expi¬ ratory grunt, and occasionally extended to the left upper extremity. The other kind of motor activity consisted of seemingly

voluntary fidgeting movements during which the patient rubbed one foot against the other. This type of movement was often preceded by a myoclonic jerk. The patient explained that he could not control the impulse for these fidgeting movements for more than a few distressing moments

when increasing "tension" in the legs became intolerable. He had no control over the myoclonic jerks. Simultaneous EMG recording showed multiple aperiodic bursts of polyclonic motor discharges involving both anterior tibialis and gastrocnemius muscles, lasting from less than one to more than eight seconds. They occurred at a frequency of 4 to 12/min with no accompanying EEG changes. The bursts disappeared within 15 minutes after the subject entered phase 1

sleep. Case 2.—The

patient, who is the 59-yearpatient 1, had complained,

old brother of since the age of 15, of restlessness and jerking movements of the legs at night, prior to and following the onset of sleep, and while relaxing in a sitting position during the day. He did not suffer insomnia. Occasionally, he experienced a crawling sensation in the legs. Polygraphie recording started at mid¬ night and lasted for two hours and 15 minutes. Motor activity of the same type as in case 1 was found. By contrast with case 1, however, the polyclonic discharges exhib¬ ited a tendency toward periodicity. While the patient was awake, they occurred at a frequency of approximately 4/min. During

stage 1 of sleep, their frequency decreased to 1/min; they were rare during stage 2 of

Explanations for moving the limbs proved difficult to give. Most of the patients alluded to an uncontrollable need disease.

sleep. No discharges were noted during the last 68 minutes of the recording, which consisted entirely of stage 2 sleep. The movements did not interrupt sleep and were not accompanied by an alteration of

to move, which could be overcome for a few

only,

and which became increas¬ ingly greater and irresistible during this time. Both the terms "voluntary" and "in¬ voluntary" were used to describe the expe¬ rience, but few said that the movements were intended to relieve the paresthesia. This, and the frequent occurrence of move¬ ments in the absence of sensory symptoms, is contrary to Ekbom's suggestion1 that the restlessness is secondary to the sensory symptoms. Myoclonic jerks occurred in 12 patients and were usually aggravated by seconds

the EEG.

Family Study Clinical data were available on 15 patients. The approximate age of onset was 14 with a range of 6 to 25 years. Notable variations in the degree and type of involvement were found. Many of the subjects were not inconvenienced by their symptoms and failed to recognize their condition as abnormal. The greatest degree of involvment occurred in the propositus who was the only member to solicit medical help. Five cases reported difficulty in

fatigue. COMMENT

third of cases of restless legs syndrome have a familial inci¬ dence,23 and it seems likely that specific questionnaires would yield a higher figure. The present study docu¬ ments a pattern of transmission most consistent with an autosomal domi¬ nant trait. The unexpected sparing of all the children of subject 8 in genera¬ tion 3 (Figure) may be only tempoAbout

falling asleep; paresthesia was reported by ten patients, but in only five was it promi¬ nent; and in only two patients did it repre¬ sent the chief complaint. In all cases, fidgeting movements of the legs occurred while lying in bed prior to falling asleep, and during the day while relaxing in a chair. In one patient, these movements were the only manifestations of the

one

Family pedigree.

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AFFECTED NO INFORMATION PROPOSITUS

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rary, since two of these children are only 14 years old. It is probable that

additional cases can also be expected in generation 5, in which the age range is from 2 to 15 years. Of interest is the absence of sensory complaints in several subjects and the prominence of myoclonus. Although sensory symptoms have sometimes been regarded as a necessary feature of the syndrome,3 others5 have indi¬ cated that these symptoms can be missing and the syndrome can take a "pure motor form." In the present family, five subjects including the propositus have denied experiencing sensory symptoms of any kind. The occurrence of myoclonus in this syndrome received little attention until Lugaresi et al6 presented polygraphic data on 16 such patients. The distinguishing feature of the myoclo¬ nus in his patients, as in ours, was its onset prior to the beginning of sleep and (as in our case 2) persistence of

myoclonic movements during stages 1 and 2 of sleep. Lugaresi et al also noted a 15- to 30-second periodicity of the myoclonus, a desynchronization of

the EEG tracing in the awake patient, and the presence of complexes prior to the onset of the movements in

relationship of restless legs with myoclonus to relaxation and sleep, as

lightly sleeping patients. Myoclonus occurring only during stages 1 and 2 of sleep6 may represent a variant of the sudden bodily jerks frequently encountered in normal subjects7 on falling asleep. Also recorded are cases in whom myoclonus is absent during wakefulness, but occurs during all four stages of sleep.89 The physiologic myoclonic twitches of De Lisi10 are limited, asynchronous, arrythmic, and asym¬

nonmyoclonic motor activity, help to distinguish it from hereditary essen¬ tial myoclonus.12 We have recently studied a patient with the "painful legs moving toes syndrome,"13 who has siblings with typical restless legs, leading us to suspect that the disor¬

metric movements that occur in normal individuals throughout the night, but mostly in stages 1 and 2. In 1953, under the title of "nocturnal myoclonus," Symonds11 described five cases characterized by myoclonic jerks occurring prior to and during sleep, which he attributed to epilepsy. The relationship between the myoclonic jerks and the stages of sleep is not known, but one of his cases (No. 4) is a typical example of restless legs, and it is possible that the others may repre¬ sent a form of the syndrome. The

well as the simultaneous occurrence of

ders are the same. No effective treatment of restless legs has been found and no cause is known. In our view, the evidence pre¬ sented in this report and in others1·2 compels us to believe that in a large number of cases, the disease is geneti¬ cally transmitted as an autosomal trait. Bruneau, MD, referred case 1. Marcel Cadotte, MD, assisted with analysis of genetic data. Jacques Montplaisir, MD, assisted in the preparation of the manuscript. André Béerens, Michel Saint-Denis, and Madeleine Dion provided Luc

assistance.

Nonproprietary Name and Trademark of Drug Carbamazepine- Tegretol.

References 1. Ekbom KA: Restless legs syndrome. Neurology 10:868-873, 1960. 2. Bornstein B: Restless legs. Psychiatry Neurol 141:165-201, 1961. 3. Ekbom KA: Restless legs. Acta Med Scand 158(suppl):1-123, 1945. 4. Dement W, Kleitman N: Cyclic variations in EEG during sleep and their relation to eye movements, body motility and dreaming. Elec-

troencephalogr

Clin

Neurophysiol 9:673-690,

1957. 5. Bonduelle M: Paresth\l=e'\sieagitante nocturne des membres inf\l=e'\rieurset impatiences. Presse

Med 60:62-64, 1952. 6. Lugaresi E, Coccagna G, Ceroni GB, et al: Restless legs syndrome and nocturnal myoclonus. Read before the 15th European Meeting on Electroencephalography, Bologna, Italy, 1967. 7. Oswald I: Sudden bodily jerks on falling asleep. Brain 82:92-103, 1959. 8. Guilleminault C, Montplaisir J, Dement WC: Nocturnal myoclonus and 5 HTP. Read before the 1974 Meeting of the Society for Neuroscience, St Louis, 1974. 9. Vazgnez de Negrotto 0, Garcia-Austt E, Gerstle de Pasquet E, et al: El sindrome de

piernas inquietas. 168, 1971.

Dagnino N, Loeb C, Massazza G et al: Hypnic physiological myoclonias in man: An EEG-EMG study in normals and neurological patients. Eur Neurol 2:47-58, 1969. 11. Symonds CP: Nocturnal myoclonus. J Neurol Neurosurg Psychiatry 16:166-171, 1953. 12. Mahloudji M, Pikielny RT: Hereditary essential myoclonus. Brain 90:669-674, 1967. 13. Spillane JD, Nathan PW, Kelly RE, et al: Painful legs and moving toes. Brain 94:541-556, 10.

1971.

Department of Fairness In recent issues of the Archives, by inadvertent typo¬ graphical error, which was not detected in time to permit correction before publication, an advertisement was published referring to a "gentile" locality. The American Medical Association deeply regrets this error and takes this opportunity to reaffirm its policy of not accepting any advertisement which indicates any unlawful discrimination on the basis of race, color, religion, national origin, or sex.

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Acta Neurol Lat Am 17:157\x=req-\

Myoclonus in familial restless legs syndrome.

Eighteen members of a family were affected over a span of five generations with the restless legs syndrome, transmitted as an autosomal dominant trait...
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